{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:10:51Z","timestamp":1760235051197,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,24]],"date-time":"2021-07-24T00:00:00Z","timestamp":1627084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Mi 294\/5-2"],"award-info":[{"award-number":["Mi 294\/5-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Neuropeptide Y (NPY) acts via multiple receptor subtypes termed Y1, Y2 and Y5. While Y1 receptor-mediated effects, e.g., in the vasculature, are often sensitive to inhibitors of L-type Ca2+ channels such as nifedipine, little is known about the role of such channels in Y5-mediated effects such as diuresis and natriuresis. Therefore, we explored whether nifedipine affects NPY-induced diuresis and natriuresis. After pre-treatment with nifedipine or vehicle, anesthetized rats received infusions or bolus injections of NPY. Infusion NPY (1 \u00b5g\/kg\/min) increased diuresis and natriuresis, and this was attenuated by intraperitoneal injection of nifedipine (3 \u00b5g\/kg). Concomitant decreases in heart rate and reductions of renal blood flow were not attenuated by nifedipine. Bolus injections of NPY (0.3, 1, 3, 10 and 30 \u03bcg\/kg) dose-dependently increased mean arterial pressure and renovascular vascular resistance; only the higher dose of nifedipine (100 \u03bcg\/kg\/min i.v.) moderately inhibited these effects. We conclude that Y5-mediated diuresis and natriuresis are more sensitive to inhibition by nifedipine than Y1-mediated renovascular effects. Whether this reflects a general sensitivity of Y5 receptor-mediated responses or is specific for diuresis and natriuresis remains to be investigated.<\/jats:p>","DOI":"10.3390\/molecules26154460","type":"journal-article","created":{"date-parts":[[2021,7,25]],"date-time":"2021-07-25T22:07:00Z","timestamp":1627250820000},"page":"4460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of Nifedipine on Renal and Cardiovascular Responses to Neuropeptide Y in Anesthetized Rats"],"prefix":"10.3390","volume":"26","author":[{"given":"Angela","family":"Bischoff","sequence":"first","affiliation":[{"name":"Arensia Exploratory Medicine GmbH, 20225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Stickan-Verf\u00fcrth","sequence":"additional","affiliation":[{"name":"Department of Nephrology and of Particle Therapy, University Hospital Essen, West German Proton Therapy Centre, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4161-8467","authenticated-orcid":false,"given":"Martin C.","family":"Michel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/0306-3623(93)90151-M","article-title":"Multiple neuropeptide Y receptors are involved in cardiovascular regulation. Peripheral and central mechanisms","volume":"24","author":"Grundemar","year":"1993","journal-title":"Gen. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0014-2999(98)00242-8","article-title":"Neuropeptide Y Y1 receptors in vascular pharmacology","volume":"349","author":"Liska","year":"1998","journal-title":"Eur. J. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s004240050538","article-title":"Renal effects of neuropeptide Y","volume":"435","author":"Bischoff","year":"1998","journal-title":"Pfl\u00fcgers Arch. Eur. J. Physiol."},{"key":"ref_4","first-page":"143","article-title":"International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY and pancreatic polypeptide receptors","volume":"50","author":"Michel","year":"1998","journal-title":"Pharmacol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1007\/BF00168634","article-title":"Effects of noradrenaline and neuropeptide Y on rat mesenteric microvessel contraction","volume":"353","author":"Chen","year":"1996","journal-title":"Naunyn Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1038\/sj.bjp.0703256","article-title":"Neuropeptide Y regulates intracellular calcium through different signalling pathways linked to a Y 1 -receptor in rat mesenteric small arteries","volume":"129","author":"Prieto","year":"2000","journal-title":"Br. J. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1038\/sj.bjp.0703484","article-title":"Effects of a selective neuropeptide Y Y1 receptor antagonist BIBP 3226 on double peaked vasoconstrictor responses to periarterial nerve stimulation in canine splenic arteries","volume":"130","author":"Yang","year":"2000","journal-title":"Br. J. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s004240050362","article-title":"Renovascular and tubular effects of neuropeptide Y are discriminated by PP56 (D-myo-inositol 1,2,6-triphosphate) in anaesthetized rats","volume":"434","author":"Bischoff","year":"1997","journal-title":"Pfl\u00fcgers Arch. Eur. J. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1046\/j.1365-2680.1997.00452.x","article-title":"Vasoconstriction of rat renal interlobar arteries by noradrenaline and neuropeptide Y","volume":"17","author":"Chen","year":"1997","journal-title":"J. Auton. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1054\/npep.1999.0755","article-title":"Vascular neuropeptide Y Y1-receptors in the rat kidney: Vasoconstrictor effects and expression of Y1-receptor mRNA","volume":"33","author":"Modin","year":"1999","journal-title":"Neuropeptides"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1681\/ASN.V1061179","article-title":"Neuropeptide Y and ATP interact to control renovascular resistance in the rat","volume":"10","author":"Oberhauser","year":"1999","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3895","DOI":"10.1111\/bph.12751","article-title":"NPY\/Y1 receptor-mediated vasoconstrictory and prolfierative effects in pulmonary hypertension","volume":"171","author":"Cnrkovic","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_13","first-page":"E131","article-title":"Distinction of NPY receptors in vitro and in vivo. I. NPY-(18-36) discriminates NPY receptor subtypes in vitro","volume":"259","author":"Michel","year":"1990","journal-title":"Am. J. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/PL00005100","article-title":"The Y1 antagonist BIBP 3226 inhibits potentiation of methoxamine-induced vasoconstriction by neuropeptide Y","volume":"356","author":"Bischoff","year":"1997","journal-title":"Naunyn Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"106810","DOI":"10.1016\/j.vph.2020.106810","article-title":"Neuropeptide Y facilitates P2X1 receptor-dependent vasoconstriction via Y1 receptor activation in small mesenteric arteries during sympathetic neurogenic responses","volume":"136","author":"Fountain","year":"2021","journal-title":"Vasc. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s00210-001-0516-8","article-title":"Effects of the neuropeptide Y Y2 antagonist BIIE0246 on sympathetic transmitter release in the pig in vivo","volume":"365","author":"Lundberg","year":"2002","journal-title":"Naunyn Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1097\/00005344-199705000-00014","article-title":"Prejunctional neuropeptide Y receptors in human kidney and atrium","volume":"29","author":"Rump","year":"1997","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s00210-004-0930-9","article-title":"Neuropeptide Y inhibits acetylcholine release in human heart atrium by activation of Y2-receptors","volume":"369","author":"Schwertfeger","year":"2004","journal-title":"Naunyn Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/0014-2999(93)90807-T","article-title":"Region-specific inhibition of potassium-evoked [3H]noradrenaline release from rat brain synaptosomes by neuropeptide Y-(13-36). Involvement of NPY receptors of the Y2 type","volume":"230","author":"Martire","year":"1993","journal-title":"Eur. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1124\/mol.106.029991","article-title":"A pair-feeding study reveals that a Y5 antagonist casus weight loss in diet-induced obese mice by modulating food intake and energy expenditure","volume":"71","author":"Mashiko","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1210\/endo.139.6.6127","article-title":"Neuropeptide Y lowers blood glucose in anaesthetized rats via a Y5 receptor subtype","volume":"139","author":"Bischoff","year":"1998","journal-title":"Endocrinology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF00167376","article-title":"G-Protein coupling and signalling of Y1-like neuropeptide Y receptors in SK-N-MC cells","volume":"344","author":"Feth","year":"1991","journal-title":"Naunyn Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0014-5793(89)81499-1","article-title":"Neuropeptide Y-induced intracellular Ca2+ increases in vascular smooth muscle","volume":"259","author":"Mihara","year":"1989","journal-title":"FEBS Lett."},{"key":"ref_24","first-page":"E880","article-title":"Neuropeptide Y mobilizes Ca++ and inhibits adenylate cyclase in human erythroleukemia cells","volume":"255","author":"Motulsky","year":"1988","journal-title":"Am. J. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1139\/y99-127","article-title":"Neuropeptide Y induced increase of cytosolic and nuclear Ca2+ in heart and vascular smooth muscle","volume":"78","author":"Jacques","year":"2000","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1111\/j.1476-5381.1995.tb17234.x","article-title":"Regional involvement of an endothelium-derived contractile factor in the vasoactive actions of neuropeptide Y in bovine isolated retinal arteries","volume":"116","author":"Prieto","year":"1995","journal-title":"Br. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1536\/ihj.27.251","article-title":"Effect of nifedipine on neuropeptide Y-induced vasoconstriction in anesthetized dogs","volume":"27","author":"Hayashi","year":"1986","journal-title":"Jpn. Heart J."},{"key":"ref_28","first-page":"1261","article-title":"Pharmacological evaluation of 1229U91, a novel high-affinity and selective neuropeptide Y-Y 1 receptor antagonist","volume":"275","author":"Hegde","year":"1995","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1046\/j.1365-201X.1996.508274000.x","article-title":"Neuropeptide Y regulates rat renal tubular Na,K-ATPase through several signaling pathways","volume":"158","author":"Ohtomo","year":"1996","journal-title":"Acta Physiol. Scand."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.neuroscience.2003.10.041","article-title":"Y2 receptor expression and inhibition of voltage-dependent Ca2+ influx into rod bipolar cell terminals","volume":"125","author":"Brecha","year":"2004","journal-title":"Neuroscience"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/S0028-3908(02)00382-9","article-title":"Functional interaction between neuropeptide Y receptors and modulation of calcium channels in the rat hippocampus","volume":"44","author":"Silva","year":"2003","journal-title":"Neuropharmacology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0196-9781(01)00346-1","article-title":"Limited signal transduction repertoire of human Y5 neuropeptide Y receptors expressed in HEC-1B cells","volume":"22","author":"Bischoff","year":"2001","journal-title":"Peptides"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1038\/sj.bjp.0701028","article-title":"Receptor subtypes Y1 and Y5 are involved in the renal effects of neuropeptide Y","volume":"120","author":"Bischoff","year":"1997","journal-title":"Br. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1113\/jphysiol.1996.sp021612","article-title":"Neuropeptide Y-enhanced diuresis and natriuresis in anaesthetized rats is independent from renal blood flow reduction","volume":"495","author":"Bischoff","year":"1996","journal-title":"J. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s002109900175","article-title":"Gender and hypertension interact to regulate neuropeptide Y responsiveness","volume":"361","author":"Bischoff","year":"2000","journal-title":"Naunyn Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_36","first-page":"704","article-title":"Indomethacin inhibits the natriuretic effects of neuropeptide Y in anesthetized rats","volume":"286","author":"Bischoff","year":"1998","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_37","first-page":"F502","article-title":"Bradykinin may be involved in neuropeptide Y-induced diuresis, natriuresis, and calciuresis","volume":"275","author":"Bischoff","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0014-2999(01)00919-0","article-title":"Pharmacology of H394\/84, a dihydropyridine neuropeptide Y Y1 receptor antagonist, in vivo","volume":"418","author":"Balmer","year":"2001","journal-title":"Eur. J. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1097\/00004872-199715120-00093","article-title":"The natriuretic effect of nifedipine gastrointestinal therapeutic system remains despite the presence of mild-to-moderate renal failure","volume":"15","author":"Campo","year":"1997","journal-title":"J. Hypertens."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1124\/jpet.103.058248","article-title":"Signal transduction underlying carbachol-induced contraction of rat urinary bladder. I. Phospholipases and Ca2+ sources","volume":"308","author":"Schneider","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1124\/jpet.103.063735","article-title":"Signal transduction underlying carbachol-induced contraction of human urinary bladder","volume":"309","author":"Schneider","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1139\/y99-121","article-title":"Neuropeptide Y enhances potassium excretion by mechanisms distinct from those contolling sodium excretion","volume":"78","author":"Bischoff","year":"2000","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s002100100446","article-title":"Nifedipine inhibits sphingosine-1-phosphate-induced renovascular contraction in vitro and in vivo","volume":"364","author":"Bischoff","year":"2001","journal-title":"Naunyn Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1124\/mol.119.118927","article-title":"New author guidelines for displaying data and reporting data analysis and statistical methods in experimental biology","volume":"97","author":"Michel","year":"2020","journal-title":"Mol. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/d41586-019-00857-9","article-title":"Scientists rise up against statistical significance","volume":"567","author":"Amrhein","year":"2019","journal-title":"Nature"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/15\/4460\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:34:20Z","timestamp":1760164460000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/15\/4460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,24]]},"references-count":45,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["molecules26154460"],"URL":"https:\/\/doi.org\/10.3390\/molecules26154460","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2021,7,24]]}}}