title: Urotensin II is a nitric oxide-dependent vasodilator and natriuretic peptide in the rat kidney.
abstract: Recent studies have indicated that urotensin II (UII), a cyclic peptide, is vasoactive and may be involved in cardiovascular dysfunctions. It remains unknown, however, whether UII plays a role in the control of renal vascular tone and tubular function. In the present study, a continuous infusion of synthetic human UII (hUII) into the renal artery (RA) in anesthetized rats was found to increase renal blood flow (RBF) and urinary water and sodium excretion (UV and UNaV) in a dose-dependent manner. At a dose of 20 ng. kg-1. min-1, it increased RBF by 20% and UV and UNaV by 94 and 109%, respectively. Nitric oxide (NO) synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) completely abolished hUII-induced increases in RBF and water/sodium excretion. In isolated, pressurized, and phenylephrine-precontracted small RA with internal diameter of approximately 200 microm, hUII produced a concentration-dependent vasodilation with a maximal response of 55% at 1.5 microM. l-NAME significantly blocked this hUII-induced vasodilation by 60%. In denuded RA, hUII had neither vasodilator nor vasoconstrictor effect. With the use of 4,5-diaminofluorescein diacetate-based fluorescence imaging analysis of NO levels, hUII (1 microM) was shown to double the NO levels within the endothelium of freshly dissected small RA, and l-NAME blocked this UII-induced production of endothelial NO. These results indicate that UII produces vasodilator and natriuretic effects in the kidney and that UII-induced vasodilation is associated with increased endothelial NO in the RA.
authors.affiliation: Deptartment of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Andrew Y
authors.initials: AY
authors.lastname: Zhang
authors.forename: Ya-Fei
authors.initials: YF
authors.lastname: Chen
authors.forename: David X
authors.initials: DX
authors.lastname: Zhang
authors.forename: Fu-Xian
authors.initials: FX
authors.lastname: Yi
authors.forename: Jenson
authors.initials: J
authors.lastname: Qi
authors.forename: Patricia
authors.initials: P
authors.lastname: Andrade-Gordon
authors.forename: Lawrence
authors.initials: L
authors.lastname: de Garavilla
authors.forename: Pin-Lan
authors.initials: PL
authors.lastname: Li
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Zou
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D045283:Natriuretic Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D014579:Urotensins / Q000494:pharmacology*; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D045283:Natriuretic Agents; D014579:Urotensins; D014665:Vasodilator Agents; D009569:Nitric Oxide; C029677:urotensin II