{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T14:16:47Z","timestamp":1793197007132,"version":"4.5.0"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T00:00:00Z","timestamp":1687219200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T00:00:00Z","timestamp":1687219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Institute for Clinical and Experimental Medicine"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Heart failure (HF) has been declared as global pandemic and current therapies are still ineffective, especially in patients that develop concurrent cardio-renal syndrome. Considerable attention has been focused on the nitric oxide (NO)\/soluble guanylyl cyclase (sGC)\/cyclic guanosine monophosphate (cGMP) pathway. In the current study, we aimed to investigate the effectiveness of sGC stimulator (BAY41-8543) with the same mode of action as vericiguat, for the treatment of heart failure (HF) with cardio-renal syndrome. As a model, we chose heterozygous Ren-2 transgenic rats (TGR), with high-output heart failure, induced by aorto-caval fistula (ACF). The rats were subjected into three experimental protocols to evaluate short-term effects of the treatment, impact on blood pressure, and finally the long-term survival lasting 210\u00a0days. As control groups, we used hypertensive sham TGR and normotensive sham HanSD rats. We have shown that the sGC stimulator effectively increased the survival of rats with HF in comparison to untreated animals. After 60\u00a0days of sGC stimulator treatment, the survival was still 50% compared to 8% in the untreated rats. One-week treatment with sGC stimulator increased the excretion of cGMP in ACF TGR (109\u2009\u00b1\u200928 nnmol\/12\u00a0h), but the ACE inhibitor decreased it (-63\u2009\u00b1\u200921 nnmol\/12\u00a0h). Moreover, sGC stimulator caused a decrease in SBP, but this effect was only temporary (day 0: 117\u2009\u00b1\u20093; day 2: 108\u2009\u00b1\u20091; day 14: 124\u2009\u00b1\u20092\u00a0mmHg). These results support the concept that sGC stimulators might represent a valuable class of drugs to battle heart failure especially with cardio-renal syndrome, but further studies are necessary.<\/jats:p>","DOI":"10.1007\/s00210-023-02561-y","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T08:02:43Z","timestamp":1687248163000},"page":"3757-3773","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The treatment with sGC stimulator improves survival of hypertensive rats in response to volume-overload induced by aorto-caval fistula"],"prefix":"10.1007","volume":"396","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4397-3991","authenticated-orcid":false,"given":"Olga","family":"Gawrys","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Huskov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"\u0160karoupkov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Honetschl\u00e4gerov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zde\u0148ka","family":"Va\u0148ourkov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So\u0148a","family":"Kikerlov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vojt\u011bch","family":"Melenovsk\u00fd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara Szeiffov\u00e1","family":"Ba\u010dov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mat\u00fa\u0161","family":"Sykora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milo\u0161","family":"T\u00e1borsk\u00fd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lud\u011bk","family":"\u010cervenka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,6,20]]},"reference":[{"key":"2561_CR1","doi-asserted-by":"publisher","unstructured":"Abassi Z, Goltsman I, Karram T, et al (2011) Aortocaval fistula in rat: A unique model of volume-overload congestive heart failure and cardiac hypertrophy. J Biomed Biotechnol 2011:729497 https:\/\/doi.org\/10.1155\/2011\/729497","DOI":"10.1155\/2011\/729497"},{"issue":"7","key":"2561_CR2","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.3390\/biomedicines10071707","volume":"10","author":"K Andelova","year":"2022","unstructured":"Andelova K, Szeiffova Bacova B, Sykora M et al (2022) Cardiac Cx43 signaling is enhanced and TGF-\u03b21\/SMAD2\/3 suppressed in response to cold acclimation and modulated by thyroid status in hairless SHRM. Biomedicines 10(7):1707. https:\/\/doi.org\/10.3390\/biomedicines10071707","journal-title":"Biomedicines"},{"key":"2561_CR3","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1056\/NEJMoa1915928","volume":"382","author":"PW Armstrong","year":"2020","unstructured":"Armstrong PW, Pieske B, Anstrom KJ et al (2020) Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med 382:1883\u20131893. https:\/\/doi.org\/10.1056\/NEJMoa1915928","journal-title":"N Engl J Med"},{"key":"2561_CR4","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1139\/cjpp-2012-0393","volume":"91","author":"T Benova","year":"2013","unstructured":"Benova T, Viczenczova C, Radosinska J et al (2013) Melatonin attenuates hypertension-related proarrhythmic myocardial maladaptation of connexin-43 and propensity of the heart to lethalarrhythmias. Can J Physiol Pharmacol 91:633\u2013639. https:\/\/doi.org\/10.1139\/cjpp-2012-0393","journal-title":"Can J Physiol Pharmacol"},{"key":"2561_CR5","doi-asserted-by":"publisher","first-page":"376","DOI":"10.3238\/arztebl.2020.0376","volume":"117","author":"D Berliner","year":"2020","unstructured":"Berliner D, H\u00e4nselmann A, Bauersachs J (2020) The treatment of heart failure with reduced ejection fraction. Dtsch Arztebl Int 117:376\u2013386. https:\/\/doi.org\/10.3238\/arztebl.2020.0376","journal-title":"Dtsch Arztebl Int"},{"key":"2561_CR6","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1097\/FJC.0000000000000749","volume":"75","author":"RM Blanton","year":"2020","unstructured":"Blanton RM (2020) cGMP Signaling and Modulation in Heart Failure. J Cardiovasc Pharmacol 75:385\u2013398. https:\/\/doi.org\/10.1097\/FJC.0000000000000749","journal-title":"J Cardiovasc Pharmacol"},{"key":"2561_CR7","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1002\/ejhf.1835","volume":"22","author":"J Cautela","year":"2020","unstructured":"Cautela J, Tartiere JM, Cohen-Solal A et al (2020) Management of low blood pressure in ambulatory heart failure with reduced ejection fraction patients. Eur J Heart Fail 22:1357\u20131365. https:\/\/doi.org\/10.1002\/ejhf.1835","journal-title":"Eur J Heart Fail"},{"key":"2561_CR8","doi-asserted-by":"publisher","first-page":"11","DOI":"10.33549\/physiolres.932842","volume":"64","author":"L \u010cervenka","year":"2015","unstructured":"\u010cervenka L, B\u00edbov\u00e1 J, Huskov\u00e1 Z et al (2015a) Combined suppression of the intrarenal and circulating vasoconstrictor Renin-ACE-ANG II axis and augmentation of the vasodilator ACE2-ANG 1-7-Mas axis attenuates the systemic hypertension in Ren-2 transgenic rats exposed to chronic hypoxia. Physiol Res 64:11\u201324","journal-title":"Physiol Res"},{"key":"2561_CR9","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1111\/1440-1681.12419","volume":"42","author":"L \u010cervenka","year":"2015","unstructured":"\u010cervenka L, Melenovsk\u00fd V, Huskov\u00e1 Z et al (2015b) Inhibition of soluble epoxide hydrolase counteracts the development of renal dysfunction and progression of congestive heart failure in Ren-2 transgenic hypertensive rats with aorto-caval fistula. Clin Exp Pharmacol Physiol 42:795\u2013807. https:\/\/doi.org\/10.1111\/1440-1681.12419","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"2561_CR10","doi-asserted-by":"publisher","first-page":"2416","DOI":"10.1093\/cvr\/cvab009","volume":"117","author":"M Ciccarelli","year":"2021","unstructured":"Ciccarelli M, Dawson D, Falcao-Pires I et al (2021) Reciprocal organ interactions during heart failure: A position paper from the ESC Working Group on Myocardial Function. Cardiovasc Res 117:2416\u20132433. https:\/\/doi.org\/10.1093\/cvr\/cvab009","journal-title":"Cardiovasc Res"},{"key":"2561_CR11","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1177\/10742484211042706","volume":"26","author":"DJ Cordwin","year":"2021","unstructured":"Cordwin DJ, Berei TJ, Pogue KT (2021) The Role of sGC Stimulators and Activators in Heart Failure With Reduced Ejection Fraction. J Cardiovasc Pharmacol Ther 26:593\u2013600. https:\/\/doi.org\/10.1177\/10742484211042706","journal-title":"J Cardiovasc Pharmacol Ther"},{"key":"2561_CR12","doi-asserted-by":"publisher","unstructured":"Curnow AC, Gonsalez SR, Gogulamudi VR, et al (2020) Low nitric oxide bioavailability increases renin production in the collecting duct. Front Physiol 11:559341  https:\/\/doi.org\/10.3389\/fphys.2020.559341","DOI":"10.3389\/fphys.2020.559341"},{"key":"2561_CR13","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1111\/bph.14153","volume":"175","author":"MJ Curtis","year":"2018","unstructured":"Curtis MJ, Alexander S, Cirino G et al (2018) Experimental design and analysis and their reporting II: updated and simplified guidance for authors and peer reviewers. Br J Pharmacol 175:987\u2013993. https:\/\/doi.org\/10.1111\/bph.14153","journal-title":"Br J Pharmacol"},{"key":"2561_CR14","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1161\/01.RES.0000148664.33695.2a","volume":"95","author":"SB Danik","year":"2004","unstructured":"Danik SB, Liu F, Zhang J et al (2004) Modulation of cardiac gap junction expression and arrhythmic susceptibility. Circ Res 95:1035\u20131041. https:\/\/doi.org\/10.1161\/01.RES.0000148664.33695.2a","journal-title":"Circ Res"},{"key":"2561_CR15","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1111\/j.1524-6175.2007.06626.x","volume":"9","author":"J D\u00edez","year":"2007","unstructured":"D\u00edez J (2007) Mechanisms of cardiac fibrosis in hypertension. J Clin Hypertens (greenwich) 9:546\u2013550. https:\/\/doi.org\/10.1111\/j.1524-6175.2007.06626.x","journal-title":"J Clin Hypertens (greenwich)"},{"key":"2561_CR16","doi-asserted-by":"crossref","unstructured":"Egan Benova T, Szeiffova Bacova B, Viczenczova C, et al (2016) MyocardiaL connexin-43 is implicated in the prevention of malignant arrhythmia in rats suffering from essential hypertension. In: Update on Essential Hypertension. IntechOpen, London","DOI":"10.5772\/63456"},{"key":"2561_CR17","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1038\/nrcardio.2017.224","volume":"15","author":"C Farah","year":"2018","unstructured":"Farah C, Michel LYM, Balligand JL (2018) Nitric oxide signalling in cardiovascular health and disease. Nat Rev Cardiol 15:292\u2013316. https:\/\/doi.org\/10.1038\/nrcardio.2017.224","journal-title":"Nat Rev Cardiol"},{"key":"2561_CR18","doi-asserted-by":"publisher","first-page":"9442","DOI":"10.1002\/anie.201302588","volume":"52","author":"M Follmann","year":"2013","unstructured":"Follmann M, Griebenow N, Hahn MG et al (2013) The chemistry and biology of soluble guanylate cyclase stimulators and activators. Angew Chemie - Int Ed 52:9442\u20139462. https:\/\/doi.org\/10.1002\/anie.201302588","journal-title":"Angew Chemie - Int Ed"},{"key":"2561_CR19","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/s41440-018-0011-y","volume":"41","author":"O Gawrys","year":"2018","unstructured":"Gawrys O, Baranowska I, Gawarecka K et al (2018) Innovative lipid-based carriers containing cationic derivatives of polyisoprenoid alcohols augment the antihypertensive effectiveness of candesartan in spontaneously hypertensive rats. Hypertens Res 41:234\u2013245. https:\/\/doi.org\/10.1038\/s41440-018-0011-y","journal-title":"Hypertens Res"},{"key":"2561_CR20","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1097\/HJH.0000000000002462","volume":"38","author":"O Gawrys","year":"2020","unstructured":"Gawrys O, Huskov\u00e1 Z, Baranowska I et al (2020) Combined treatment with epoxyeicosatrienoic acid analog and 20-hydroxyeicosatetraenoic acid antagonist provides substantial hypotensive effect in spontaneously hypertensive rats. J Hypertens 38:1802\u20131810. https:\/\/doi.org\/10.1097\/HJH.0000000000002462","journal-title":"J Hypertens"},{"key":"2561_CR21","doi-asserted-by":"publisher","first-page":"e895","DOI":"10.1161\/CIR.0000000000001063","volume":"145","author":"PA Heidenreich","year":"2022","unstructured":"Heidenreich PA, Bozkurt B, Aguilar D et al (2022) 2022 AHA\/ACC\/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 145:e895\u2013e1032. https:\/\/doi.org\/10.1161\/CIR.0000000000001063","journal-title":"Circulation"},{"key":"2561_CR22","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1080\/10641963.2021.1907398","volume":"43","author":"Z Honetschlagerov\u00e1","year":"2021","unstructured":"Honetschlagerov\u00e1 Z, \u0160karoupkov\u00e1 P, Kikerlov\u00e1 S et al (2021) Effects of renal sympathetic denervation on the course of congestive heart failure combined with chronic kidney disease: Insight from studies with fawn-hooded hypertensive rats with volume overload induced using aorto-caval fistula. Clin Exp Hypertens 43:522\u2013535. https:\/\/doi.org\/10.1080\/10641963.2021.1907398","journal-title":"Clin Exp Hypertens"},{"issue":"12","key":"2561_CR23","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.3390\/biomedicines9121803","volume":"9","author":"Z Honetschl\u00e4gerov\u00e1","year":"2021","unstructured":"Honetschl\u00e4gerov\u00e1 Z, Hejnov\u00e1 L, Novotn\u00fd J et al (2021) Effects of renal denervation on the enhanced renal vascular responsiveness to angiotensin II in high-output heart failure: Angiotensin II receptor binding assessment and functional studies in ren-2 transgenic hypertensive rats. Biomedicines 9(12):1803. https:\/\/doi.org\/10.3390\/biomedicines9121803","journal-title":"Biomedicines"},{"key":"2561_CR24","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1159\/000092981","volume":"29","author":"Z Huskov\u00e1","year":"2006","unstructured":"Huskov\u00e1 Z, Kramer HJ, Thumov\u00e1 M et al (2006) Effects of anesthesia on plasma and kidney ANG II levels in normotensive and ANG II-dependent hypertensive rats. Kidney Blood Press Res 29:74\u201383. https:\/\/doi.org\/10.1159\/000092981","journal-title":"Kidney Blood Press Res"},{"key":"2561_CR25","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1159\/000099028","volume":"30","author":"Z Huskov\u00e1","year":"2007","unstructured":"Huskov\u00e1 Z, Kramer H, Va\u0148ourkov\u00e1 Z et al (2007) Effects of dietary salt load and salt depletion on the course of hypertension and angiotensin II levels in male and female heterozygous Ren-2 transgenic rats. Kidney Blood Press Res 30:45\u201355. https:\/\/doi.org\/10.1159\/000099028","journal-title":"Kidney Blood Press Res"},{"key":"2561_CR26","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1111\/1440-1681.12553","volume":"43","author":"Z Huskov\u00e1","year":"2016","unstructured":"Huskov\u00e1 Z, Kopkan L, \u010cervenkov\u00e1 L et al (2016) Intrarenal alterations of the angiotensin-converting enzyme type 2\/angiotensin 1\u20137 complex of the renin-angiotensin system do not alter the course of malignant hypertension in Cyp1a1-Ren-2 transgenic rats. Clin Exp Pharmacol Physiol 43:438\u2013449. https:\/\/doi.org\/10.1111\/1440-1681.12553","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"2561_CR27","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1097\/HJH.0000000000003307","volume":"41","author":"P Kala","year":"2023","unstructured":"Kala P, Gawrys O, Miklovi\u010d M et al (2023) Endothelin type A receptor blockade attenuates aorto-caval fistula-induced heart failure in rats with angiotensin II-dependent hypertension. J Hypertens 41:99\u2013114. https:\/\/doi.org\/10.1097\/HJH.0000000000003307","journal-title":"J Hypertens"},{"key":"2561_CR28","doi-asserted-by":"publisher","unstructured":"Kala P, Miklovi\u010d M, J\u00edchov\u00e1 \u0160, et al (2021) Effects of epoxyeicosatrienoic acid-enhancing therapy on the course of congestive heart failure in angiotensin ii-dependent rat hypertension: From mrna analysis towards functional in vivo evaluation. Biomedicines 9(8):1053 https:\/\/doi.org\/10.3390\/biomedicines9081053","DOI":"10.3390\/biomedicines9081053"},{"key":"2561_CR29","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.1159\/000495391","volume":"43","author":"V Kratky","year":"2018","unstructured":"Kratky V, Kopkan L, Kikerlova S et al (2018) The role of renal vascular reactivity in the development of renal dysfunction in compensated and decompensated congestive heart failure. Kidney Blood Press Res 43:1730\u20131741. https:\/\/doi.org\/10.1159\/000495391","journal-title":"Kidney Blood Press Res"},{"key":"2561_CR30","doi-asserted-by":"publisher","first-page":"4271","DOI":"10.1038\/s41598-021-83906-6","volume":"11","author":"V Kratky","year":"2021","unstructured":"Kratky V, Vanourkova Z, Sykora M et al (2021) AT1 receptor blocker, but not an ACE inhibitor, prevents kidneys from hypoperfusion during congestive heart failure in normotensive and hypertensive rats. Sci Rep 11:4271. https:\/\/doi.org\/10.1038\/s41598-021-83906-6","journal-title":"Sci Rep"},{"issue":"6","key":"2561_CR31","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.3390\/ijms19061712","volume":"19","author":"SM Krishnan","year":"2018","unstructured":"Krishnan SM, Kraehling JR, Eitner F et al (2018) The impact of the nitric oxide (no)\/soluble guanylyl cyclase (sGC) signaling cascade on kidney health and disease: A preclinical perspective. Int J Mol Sci 19(6):1712. https:\/\/doi.org\/10.3390\/ijms19061712","journal-title":"Int J Mol Sci"},{"key":"2561_CR32","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1111\/1440-1681.12204","volume":"41","author":"P Kujal","year":"2014","unstructured":"Kujal P, \u010cert\u00edkov\u00e1 Ch\u00e1bov\u00e1 V, \u0160karoupkov\u00e1 P et al (2014) Inhibition of soluble epoxide hydrolase is renoprotective in 5\/6 nephrectomized Ren-2 transgenic hypertensive rats. Clin Exp Pharmacol Physiol 41:227\u2013237. https:\/\/doi.org\/10.1111\/1440-1681.12204","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"2561_CR33","doi-asserted-by":"publisher","first-page":"F849","DOI":"10.1152\/ajprenal.1998.275.6.f849","volume":"275","author":"A Kurtz","year":"1998","unstructured":"Kurtz A, Wagner C (1998) Role of nitric oxide in the control of renin secretion. Am J Physiol - Ren Physiol 275:F849\u2013F862. https:\/\/doi.org\/10.1152\/ajprenal.1998.275.6.f849","journal-title":"Am J Physiol - Ren Physiol"},{"key":"2561_CR34","doi-asserted-by":"publisher","unstructured":"Lam CSP, Mulder H, Lopatin Y et al (2021) Blood pressure and safety events with vericiguat in the VICTORIA trial. J Am Heart Assoc 10(22):e021094 https:\/\/doi.org\/10.1161\/JAHA.121.021094","DOI":"10.1161\/JAHA.121.021094"},{"key":"2561_CR35","doi-asserted-by":"publisher","first-page":"5492","DOI":"10.1038\/s41467-021-25617-0","volume":"12","author":"R Liu","year":"2021","unstructured":"Liu R, Kang Y, Chen L (2021) Activation mechanism of human soluble guanylate cyclase by stimulators and activators. Nat Commun 12:5492. https:\/\/doi.org\/10.1038\/s41467-021-25617-0","journal-title":"Nat Commun"},{"key":"2561_CR36","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1007\/BF00496137","volume":"49","author":"Z Lojda","year":"1976","unstructured":"Lojda Z, Gutmann E (1976) Histochemistry of some acid hydrolases in striated muscles of the rat. Histochemistry 49:337\u2013342. https:\/\/doi.org\/10.1007\/BF00496137","journal-title":"Histochemistry"},{"key":"2561_CR37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1161\/JAHA.121.024139","volume":"11","author":"PA McCullough","year":"2022","unstructured":"McCullough PA, Amin A, Pantalone KM, Ronco C (2022) Cardiorenal Nexus: A Review With Focus on Combined Chronic Heart and Kidney Failure, and Insights From Recent Clinical Trials. J Am Heart Assoc 11:1\u20139. https:\/\/doi.org\/10.1161\/JAHA.121.024139","journal-title":"J Am Heart Assoc"},{"key":"2561_CR38","doi-asserted-by":"publisher","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","volume":"42","author":"TA McDonagh","year":"2021","unstructured":"McDonagh TA, Metra M, Adamo M et al (2021) 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 42:3599\u20133726. https:\/\/doi.org\/10.1093\/eurheartj\/ehab368","journal-title":"Eur Heart J"},{"key":"2561_CR39","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1159\/000331562","volume":"35","author":"V Melenovsky","year":"2012","unstructured":"Melenovsky V, Skaroupkova P, Benes J et al (2012) The course of heart failure development and mortality in rats with volume overload due to aorto-caval fistula. Kidney Blood Press Res 35:167\u2013173. https:\/\/doi.org\/10.1159\/000331562","journal-title":"Kidney Blood Press Res"},{"key":"2561_CR40","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1093\/eurheartj\/ehx035","volume":"38","author":"W Mullens","year":"2017","unstructured":"Mullens W, Verbrugge FH, Nijst P, Tang WHW (2017) Renal sodium avidity in heart failure: From pathophysiology to treatment strategies. Eur Heart J 38:1872\u20131882. https:\/\/doi.org\/10.1093\/eurheartj\/ehx035","journal-title":"Eur Heart J"},{"key":"2561_CR41","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1001\/jama.2020.10262","volume":"324","author":"SP Murphy","year":"2020","unstructured":"Murphy SP, Ibrahim NE, Januzzi JL (2020) Heart Failure with Reduced Ejection Fraction: A Review. JAMA - J Am Med Assoc 324:488\u2013504. https:\/\/doi.org\/10.1001\/jama.2020.10262","journal-title":"JAMA - J Am Med Assoc"},{"key":"2561_CR42","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1111\/j.1440-1827.2008.02237.x","volume":"58","author":"Y Nakano","year":"2008","unstructured":"Nakano Y, Hirano T, Uehara K et al (2008) New rat model induced by anti-glomerular basement membrane antibody shows severe glomerular adhesion in early stage and quickly progresses to end-stage renal failure. Pathol Int 58:361\u2013370. https:\/\/doi.org\/10.1111\/j.1440-1827.2008.02237.x","journal-title":"Pathol Int"},{"key":"2561_CR43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fphar.2022.792798","volume":"13","author":"G Numata","year":"2022","unstructured":"Numata G, Takimoto E (2022) Cyclic GMP and PKG Signaling in Heart Failure. Front Pharmacol 13:1\u201311. https:\/\/doi.org\/10.3389\/fphar.2022.792798","journal-title":"Front Pharmacol"},{"key":"2561_CR44","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1093\/eurheartj\/ehx026","volume":"38","author":"W Ouwerkerk","year":"2017","unstructured":"Ouwerkerk W, Voors AA, Anker SD et al (2017) Determinants and clinical outcome of uptitration of ACE-inhibitors and beta-blockers in patients with heart failure: A prospective European study. Eur Heart J 38:1883\u20131890. https:\/\/doi.org\/10.1093\/eurheartj\/ehx026","journal-title":"Eur Heart J"},{"key":"2561_CR45","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/BF00926360","volume":"129","author":"V Pelouch","year":"1993","unstructured":"Pelouch V, Dixon IMC, Sethi R, Dhalla NS (1993) Alteration of collagenous protein profile in congestive heart failure secondary to myocardial infarction. Mol Cell Biochem 129:121\u2013131. https:\/\/doi.org\/10.1007\/BF00926360","journal-title":"Mol Cell Biochem"},{"key":"2561_CR46","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1113\/jphysiol.2003.049890","volume":"552","author":"PB Persson","year":"2003","unstructured":"Persson PB (2003) Renin: Origin, secretion and synthesis. J Physiol 552:667\u2013671. https:\/\/doi.org\/10.1113\/jphysiol.2003.049890","journal-title":"J Physiol"},{"key":"2561_CR47","doi-asserted-by":"publisher","first-page":"E840","DOI":"10.1161\/CIR.0000000000000664","volume":"139","author":"J Rangaswami","year":"2019","unstructured":"Rangaswami J, Bhalla V, Blair JEA et al (2019) Cardiorenal Syndrome: Classification, Pathophysiology, Diagnosis, and Treatment Strategies: A Scientific Statement From the American Heart Association. Circulation 139:E840\u2013E878. https:\/\/doi.org\/10.1161\/CIR.0000000000000664","journal-title":"Circulation"},{"key":"2561_CR48","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/0009-9120(96)00003-6","volume":"29","author":"GK Reddy","year":"1996","unstructured":"Reddy GK, Enwemeka CS (1996) A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem 29:225\u2013229. https:\/\/doi.org\/10.1016\/0009-9120(96)00003-6","journal-title":"Clin Biochem"},{"key":"2561_CR49","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.1093\/cvr\/cvz161","volume":"115","author":"C Riehle","year":"2019","unstructured":"Riehle C, Bauersachs J (2019) Small animal models of heart failure. Cardiovasc Res 115:1838\u20131849. https:\/\/doi.org\/10.1093\/cvr\/cvz161","journal-title":"Cardiovasc Res"},{"key":"2561_CR50","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.2174\/138945012802002348","volume":"13","author":"B Roberto","year":"2012","unstructured":"Roberto B, Evora P, M. Evora P, C. Celotto A, et al (2012) Cardiovascular Therapeutics Targets on the NO\u2013sGC\u2013cGMP Signaling Pathway: A Critical Overview. Curr Drug Targets 13:1207\u20131214. https:\/\/doi.org\/10.2174\/138945012802002348","journal-title":"Curr Drug Targets"},{"key":"2561_CR51","doi-asserted-by":"publisher","unstructured":"Sandner P, Follmann M, Becker-Pelster E et al (2021a) Soluble GC stimulators and activators: Past, present and future. Br J Pharmacol Oct 2:1\u201322. https:\/\/doi.org\/10.1111\/bph.15698","DOI":"10.1111\/bph.15698"},{"key":"2561_CR52","doi-asserted-by":"crossref","unstructured":"Sandner P, Zimmer DP, Milne GT et al (2021b) Soluble guanylate cyclase stimulators and activators.  In: Schmidt HHHW, Ghezzi P, Cuadrado A (eds) Reactive Oxygen Species. Handbook of Experimental Pharmacology, vol. 264. Springer, Cham, pp 355\u2013394","DOI":"10.1007\/164_2018_197"},{"key":"2561_CR53","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1177\/41.12.8245430","volume":"41","author":"S Schultz-Hector","year":"1993","unstructured":"Schultz-Hector S, Balz K, Bohm M et al (1993) Cellular localization of endothelial alkaline phosphatase reaction product and enzyme protein in the myocardium. J Histochem Cytochem 41:1813\u20131821. https:\/\/doi.org\/10.1177\/41.12.8245430","journal-title":"J Histochem Cytochem"},{"key":"2561_CR54","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1080\/10641963.2016.1235184","volume":"39","author":"L Sedl\u00e1kov\u00e1","year":"2017","unstructured":"Sedl\u00e1kov\u00e1 L, \u010cert\u00edkov\u00e1 Ch\u00e1bov\u00e1 V, Dole\u017eelov\u00e1 \u0160 et al (2017) Renin\u2013angiotensin system blockade alone or combined with ETA receptor blockade: effects on the course of chronic kidney disease in 5\/6 nephrectomized Ren-2 transgenic hypertensive rats. Clin Exp Hypertens 39:183\u2013195. https:\/\/doi.org\/10.1080\/10641963.2016.1235184","journal-title":"Clin Exp Hypertens"},{"key":"2561_CR55","doi-asserted-by":"publisher","first-page":"1666","DOI":"10.1097\/HJH.0b013e32833b558c","volume":"28","author":"Y Sharkovska","year":"2010","unstructured":"Sharkovska Y, Kalk P, Lawrenz B et al (2010) Nitric oxide-independent stimulation of soluble guanylate cyclase reduces organ damage in experimental low-renin and high-renin models. J Hypertens 28:1666\u20131675. https:\/\/doi.org\/10.1097\/HJH.0b013e32833b558c","journal-title":"J Hypertens"},{"key":"2561_CR56","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.jacbts.2021.10.018","volume":"7","author":"A Sharma","year":"2022","unstructured":"Sharma A, Verma S, Bhatt DL et al (2022) Optimizing Foundational Therapies in Patients With HFrEF: How Do We Translate These Findings Into Clinical Care? JACC Basic to Transl Sci 7:504\u2013517. https:\/\/doi.org\/10.1016\/j.jacbts.2021.10.018","journal-title":"JACC Basic to Transl Sci"},{"key":"2561_CR57","doi-asserted-by":"publisher","unstructured":"Simmonds SJ, Cuijpers I, Heymans S, Jones EAV (2020) Cellular and molecular differences between HFpEF and HFrEF: a step ahead in an improved pathological understanding. Cells 9(1):242.\u00a0https:\/\/doi.org\/10.3390\/cells9010242","DOI":"10.3390\/cells9010242"},{"key":"2561_CR58","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1007\/s11897-018-0383-y","volume":"15","author":"P Singh","year":"2018","unstructured":"Singh P, Vijayakumar S, Kalogeroupoulos A, Butler J (2018) Multiple Avenues of Modulating the Nitric Oxide Pathway in Heart Failure Clinical Trials. Curr Heart Fail Rep 15:44\u201352. https:\/\/doi.org\/10.1007\/s11897-018-0383-y","journal-title":"Curr Heart Fail Rep"},{"key":"2561_CR59","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1161\/HYPERTENSIONAHA.121.17360","volume":"78","author":"P Sobieraj","year":"2021","unstructured":"Sobieraj P, Nilsson PM, Kahan T (2021) Heart Failure Events in a Clinical Trial on Arterial Hypertension: New Insights into the SPRINT Trial. Hypertension 78:1241\u20131247. https:\/\/doi.org\/10.1161\/HYPERTENSIONAHA.121.17360","journal-title":"Hypertension"},{"key":"2561_CR60","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1111\/1440-1681.12310","volume":"41","author":"A Sporkov\u00e1","year":"2014","unstructured":"Sporkov\u00e1 A, J\u00edchov\u00e1 S, Huskov\u00e1 Z et al (2014) Different mechanisms of acute versus long-term antihypertensive effects of soluble epoxide hydrolase inhibition: studies in Cyp1a1-Ren-2 transgenic rats. Clin Exp Pharmacol Physiol 41:1003\u20131013. https:\/\/doi.org\/10.1111\/1440-1681.12310","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"2561_CR61","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1038\/35065611","volume":"410","author":"JP Stasch","year":"2001","unstructured":"Stasch JP, Becker EM, Alonso-Alija C et al (2001) NO-independent regulatory site on soluble guanylate cyclase. Nature 410:212\u2013215. https:\/\/doi.org\/10.1038\/35065611","journal-title":"Nature"},{"key":"2561_CR62","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/sj.bjp.0704484","volume":"135","author":"JP Stasch","year":"2002","unstructured":"Stasch JP, Alonso-Alija C, Apeler H et al (2002a) Pharmacological actions of a novel NO-independent guanylyl cyclase stimulator, BAY 41\u20138543: In vitro studies. Br J Pharmacol 135:333\u2013343. https:\/\/doi.org\/10.1038\/sj.bjp.0704484","journal-title":"Br J Pharmacol"},{"key":"2561_CR63","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/sj.bjp.0704483","volume":"135","author":"JP Stasch","year":"2002","unstructured":"Stasch JP, Dembowsky K, Perzborn E et al (2002b) Cardiovascular actions of a novel NO-independent guanylyl cyclase stimulator, BAY 41\u20138543: In vivo studies. Br J Pharmacol 135:344\u2013355. https:\/\/doi.org\/10.1038\/sj.bjp.0704483","journal-title":"Br J Pharmacol"},{"key":"2561_CR64","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.coph.2014.12.014","volume":"21","author":"JP Stasch","year":"2015","unstructured":"Stasch JP, Schlossmann J, Hocher B (2015) Renal effects of soluble guanylate cyclase stimulators and activators: A review of the preclinical evidence. Curr Opin Pharmacol 21:95\u2013104. https:\/\/doi.org\/10.1016\/j.coph.2014.12.014","journal-title":"Curr Opin Pharmacol"},{"key":"2561_CR65","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1139\/cjpp-2018-0740","volume":"97","author":"M Sykora","year":"2019","unstructured":"Sykora M, Kamocsaiova L, Egan Benova T et al (2019) Alterations in myocardial connexin-43 and matrix metalloproteinase-2 signaling in response to pregnancy and oxygen deprivation of wistar rats: A pilot study. Can J Physiol Pharmacol 97:829\u2013836. https:\/\/doi.org\/10.1139\/cjpp-2018-0740","journal-title":"Can J Physiol Pharmacol"},{"key":"2561_CR66","doi-asserted-by":"publisher","first-page":"3490","DOI":"10.3390\/ijms24043490","volume":"24","author":"M Sykora","year":"2023","unstructured":"Sykora M, Kratky V, Kopkan L, Tribulova N (2023) Anti-Fibrotic Potential of Angiotensin (1\u20137) in Hemodynamically Overloaded Rat Heart. Int J Mol Sci 24:3490. https:\/\/doi.org\/10.3390\/ijms24043490","journal-title":"Int J Mol Sci"},{"key":"2561_CR67","doi-asserted-by":"publisher","unstructured":"Szeiffov\u00e1 Ba\u010dova B, Egan Be\u0148ov\u00e1 T, Viczenczov\u00e1 C, et al (2016) Cardiac connexin-43 and PKC signaling in rats with altered thyroid status without and with omega-3 fatty acids intake. Physiol Res 65 Suppl 1:S77\u201390 https:\/\/doi.org\/10.33549\/physiolres.933413","DOI":"10.33549\/physiolres.933413"},{"key":"2561_CR68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.biopha.2022.112894","volume":"149","author":"J Xia","year":"2022","unstructured":"Xia J, Hui N, Tian L et al (2022) Development of vericiguat: The first soluble guanylate cyclase (sGC) stimulator launched for heart failure with reduced ejection fraction (HFrEF). Biomed Pharmacother 149:1\u201312. https:\/\/doi.org\/10.1016\/j.biopha.2022.112894","journal-title":"Biomed Pharmacother"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-023-02561-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-023-02561-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-023-02561-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T02:04:33Z","timestamp":1699841073000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-023-02561-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,20]]},"references-count":68,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["2561"],"URL":"https:\/\/doi.org\/10.1007\/s00210-023-02561-y","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2745368\/v1","asserted-by":"object"}]},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,20]]},"assertion":[{"value":"28 March 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was performed in accordance with guidelines and practices established by the Animal Care and Use Committee of the Institute for Clinical and Experimental Medicine (Prague) approved by the Ministry of Health of the Czech Republic, which accords with the European Union Directive 63\/2010 and ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}