{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T15:06:09Z","timestamp":1771081569011,"version":"3.50.1"},"reference-count":56,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Heart failure (HF) with a mildly reduced ejection fraction (HFmrEF; 40%\u201349%) is present in \u226425% of HF patients. Therapeutic treatment options for HFmrEF\u2010associated exercise intolerance are limited. Nitric oxide (NO)\u2010independent stimulation of soluble guanylyl cyclase to improve peripheral vasodilatation offers a novel approach to enhance skeletal muscle oxygenation (interstitial pressure of O\n                    <jats:sub>2<\/jats:sub>\n                    ) and exercise capacity. We tested the hypotheses that the soluble guanylyl cyclase stimulator BAY 41\u20102272 (BAY41) would increase exercise tolerance, skeletal muscle interstitial pressure of O\n                    <jats:sub>2<\/jats:sub>\n                    during contractions and NO sensitivity in rats with HFmrEF. Healthy Sprague\u2013Dawley rats (\n                    <jats:italic>n\u00a0<\/jats:italic>\n                    =\u00a020) and rats with experimentally induced HFmrEF (\n                    <jats:italic>n\u00a0<\/jats:italic>\n                    =\u00a025) (3\u20134 months old) were used for this investigation. HFmrEF was confirmed via echocardiography, and rats were randomized and treated with 1.0\u00a0mg\/kg of BAY41 or vehicle for 2\u00a0weeks, followed by exercise testing and spinotrapezius muscle phosphorescence quenching measurements during 1\u00a0Hz contractions. The HFmrEF rats had a lower exercise capacity than healthy rats (834\u00a0\u00b1\u00a0169\u00a0vs. 1138\u00a0\u00b1\u00a0214\u00a0s;\n                    <jats:italic>p\u00a0<\/jats:italic>\n                    &lt;\u00a00.001). BAY41 increased exercise capacity (1158\u00a0\u00b1\u00a0223\u00a0s;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.006) and muscle oxygenation index (1461\u00a0\u00b1\u00a0427\u00a0vs. 1108\u00a0\u00b1\u00a0239\u00a0mmHg\u00b7s;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.047) during 1\u00a0Hz contractions versus HFmrEF vehicle control rats. Sodium nitroprusside superfusion elicited a faster response time in BAY41\u2010treated HFmrEF rats versus vehicle\u2010treated control animals (150\u00a0\u00b1\u00a058\u00a0vs. 220\u00a0\u00b1\u00a050\u00a0s;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.022). After sodium nitroprusside superfusion, BAY41\u2010treated HFmrEF rats had a significantly elevated muscle oxygenation index during steady\u2010state contractions versus vehicle\u2010treated control animals (3104\u00a0\u00b1\u00a0703\u00a0vs. 2365\u00a0\u00b1\u00a0682\u00a0mmHg\u00b7s;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.027). These data suggest that stimulation with soluble guanylyl cyclase can improve skeletal muscle oxygenation and increase the exercise capacity in HFmrEF rats, potentially via enhanced vascular smooth muscle NO sensitivity.\n                  <\/jats:p>","DOI":"10.1113\/ep092756","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T02:39:21Z","timestamp":1750387161000},"page":"474-488","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of soluble guanylyl cyclase stimulation on muscle oxygenation and exercise capacity in heart failure with mildly reduced ejection fraction"],"prefix":"10.1113","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5110-270X","authenticated-orcid":false,"given":"Ramona E.","family":"Weber","sequence":"first","affiliation":[{"name":"Department of Kinesiology Kansas State University  Manhattan Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6467-5179","authenticated-orcid":false,"given":"Kiana M.","family":"Schulze","sequence":"additional","affiliation":[{"name":"Department of Kinesiology Kansas State University  Manhattan Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew G.","family":"Horn","sequence":"additional","affiliation":[{"name":"Department of Kinesiology Kansas State University  Manhattan Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler E.","family":"McCoach","sequence":"additional","affiliation":[{"name":"Department of Kinesiology Kansas State University  Manhattan Kansas USA"},{"name":"University of Kansas School of Medicine  Kansas City Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2591-6002","authenticated-orcid":false,"given":"Zachary J.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Anatomy &amp; Physiology Kansas State University  Manhattan Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. Sue","family":"Hageman","sequence":"additional","affiliation":[{"name":"Department of Anatomy &amp; Physiology Kansas State University  Manhattan Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8962-8475","authenticated-orcid":false,"given":"Stephanie E.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Anatomy &amp; Physiology Kansas State University  Manhattan Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Sandner","sequence":"additional","affiliation":[{"name":"Bayer HealthCare AG, Drug Discovery  Wuppertal Germany"},{"name":"Institute of Pharmacology, Hannover Medical School  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brad J.","family":"Behnke","sequence":"additional","affiliation":[{"name":"Department of Kinesiology Kansas State University  Manhattan Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy I.","family":"Musch","sequence":"additional","affiliation":[{"name":"Department of Kinesiology Kansas State University  Manhattan Kansas USA"},{"name":"Department of Anatomy &amp; Physiology Kansas State University  Manhattan Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2441-3793","authenticated-orcid":false,"given":"David C.","family":"Poole","sequence":"additional","affiliation":[{"name":"Department of Kinesiology Kansas State University  Manhattan Kansas USA"},{"name":"Department of Anatomy &amp; Physiology Kansas State University  Manhattan Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1915928"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.6.H3131"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(01)00195-5"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00388.2005"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.2115"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2016_100"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.121.009337"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.813"},{"issue":"2","key":"e_1_2_9_10_1","first-page":"425","article-title":"Muscle and liver glycogen content: Diurnal variation and endurance","volume":"47","author":"Clark J. H.","year":"1979","journal-title":"Journal of Applied Physiology\u2010Respiratory, Environmental and Exercise Physiology"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.91566.2008"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.198382"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00164.2019"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01022.2017"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1996.80.1.261"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-050410-100030"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac2022234"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.06.025"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.2006.01598.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209657"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-2862(73)90055-1"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.20739"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000012748.58444.08"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2012.11.006"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8235"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1992.73.2.728"},{"issue":"11","key":"e_1_2_9_27_1","first-page":"763","article-title":"Heart failure with mid\u2010range (borderline) ejection fraction: Clinical implications and future directions","volume":"5","author":"Hsu J. J.","year":"2017","journal-title":"Journal of the American College of Cardiology Heart Failure"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1112123"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000002470"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2014-305538"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(96)00204-5"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1999.87.2.652"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00355.2004"},{"issue":"3","key":"e_1_2_9_34_1","first-page":"S67","article-title":"Endothelial control of vascular tone in chronic heart failure","volume":"32","author":"Kiowski W.","year":"1998","journal-title":"Journal of Cardiovascular Pharmacology"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.84.4.1589"},{"issue":"6","key":"e_1_2_9_36_1","first-page":"706","article-title":"Clinical outcomes and response to vericiguat according to index heart failure event: Insights from the VICTORIA trial","volume":"6","author":"Lam C. S. P.","year":"2021","journal-title":"Journal of the American Medical Association Cardiology"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1997.83.4.1318"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.114.001504"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.04.060"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2016.6630"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0700982"},{"issue":"2","key":"e_1_2_9_42_1","first-page":"H411","article-title":"Skeletal muscle blood flow abnormalities in rats with a chronic myocardial infarction: Rest and exercise","volume":"262","author":"Musch T. I.","year":"1992","journal-title":"The American Journal of Physiology"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.454"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1997.272.2.C501"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2008.12.010"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.44.4.503"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00697.2019"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00943.2011"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/ehjci\/jez014"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.85.6.534"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543776.2021.1866538"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1177\/2047487317739079"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvac013"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-021-00605-5"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1113\/EP089631"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-68964-5_13"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2021.12.001"}],"container-title":["Experimental Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP092756","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/EP092756","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP092756","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T14:19:07Z","timestamp":1771078747000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/EP092756"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,19]]},"references-count":56,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1113\/EP092756"],"URL":"https:\/\/doi.org\/10.1113\/ep092756","archive":["Portico"],"relation":{},"ISSN":["0958-0670","1469-445X"],"issn-type":[{"value":"0958-0670","type":"print"},{"value":"1469-445X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,19]]},"assertion":[{"value":"2025-03-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}