title: The angiotensin receptor antagonist 2-ethoxy-1-[[2'-(1H- tetrazol-5-yl) biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylic acid (CV11974) attenuates the tubuloglomerular feedback response during NO synthase blockade in rats.
abstract: Nitric oxide (NO) produced in the juxtaglomerular apparatus may regulate the tubuloglomerular feedback (TGF) response. The inhibition of intrinsic NO results in significant renal hemodynamic changes, a phenomenon similar to that observed after angiotensin II (A-II) administration. We measured stop-flow pressure (Psf) during loop perfusion with artificial tubular fluid in Sprague-Dawley rats to establish whether alterations in TGF responsiveness during NO inhibition depend on the action of endogenous A-II. The NO synthase blocker N omega-nitro-L-arginine-methyl-ester (L-NAME: 10 mg/kg i.v.) significant increased TGF responsiveness, defined as the change in Psf on increasing loop flow from 0 to 40 nl/min compared with control (delta Psf: -21.3 +/- 2.6 vs. -9.7 +/- 0.6 mm Hg, P < .001). After concomitant treatment with the nonpeptide A-II type 1 receptor antagonist 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxic acid (CV11974: 1 mg/kg i.v.) and L-NAME, the TGF response was attenuated significantly (delta Psf: -7.6 +/- 1.9 mm Hg, P < .001). On the other hand, Psf in the absence of loop perfusion was increased similarly by L-NAME treatment in the presence (53.7 +/- 2.2 mm Hg) or absence of CV11974 (Psf 50.7 +/- 3.2 mm Hg). These results suggest that augmentation of the TGF response by endogenous NO inhibition depends, at least in part, on the intrinsic A-II activity.
authors.affiliation: Department of Internal Medicine II, School of Medicine, Hokkaido University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kawata
authors.forename: S
authors.initials: S
authors.lastname: Hashimoto
authors.forename: T
authors.initials: T
authors.lastname: Koike
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D005246:Feedback; D006439:Hemodynamics / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000502:physiology; D007684:Kidney Tubules / Q000187:drug effects* / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000804:Angiotensin II; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; C081643:candesartan; D019331:NG-Nitroarginine Methyl Ester