title: Blunted tubuloglomerular feedback by absence of angiotensin type 1A receptor involves neuronal NOS.
abstract: To define the role of angiotensin type 1A (AT1A) receptor in modulating tubuloglomerular feedback signals and to determine its relationship to neuronal NO synthase (nNOS), the diameter of the afferent arterioles of wild-type and AT1A receptor-deficient mice was measured by the blood-perfused juxtamedullary nephron technique. The afferent arteriolar diameter of wild-type and AT1A receptor-deficient mice averaged 16.7+/-0.6 (n=9) and 16.8+/-0.7 micro m (n=9), respectively. In the wild-type mice, addition of 10 micro mol/L acetazolamide to the blood perfusate exerted a biphasic afferent arteriolar constriction, with the initial response and sustained response averaging 47.2+/-3.8% and 33.9+/-3.3%, respectively. In AT1A receptor-deficient mice, the initial response and sustained response averaged 51.6+/-3.6% and 9.5+/-1.3%, respectively, and the sustained response was significantly attenuated compared with that of wild-type mice. Inhibition of nNOS with 10 micro mol/L S-methyl-L-thiocitrulline significantly decreased the afferent arteriolar diameter of AT1A receptor-deficient mice, from 15.1+/-1.2 to 5.0+/-0.3 micro m (n=7), and the decrease was significantly greater than that observed in wild-type mice (from 15.9+/-1.2 to 10.6+/-1.3 micro m; n=8). During nNOS inhibition, the initial and sustained afferent arteriolar constrictor responses to acetazolamide in wild-type mice averaged 54.4+/-6.4% and 44.8+/-11.3%; respectively, and were similar to those in AT1A receptor-deficient mice (53.2+/-6.4% and 59.5+/-4.4%, respectively). These results suggest that AT1A receptors enhance tubuloglomerular feedback-mediated afferent arteriolar constriction, at least in part, through reducing the counteracting modulation by nNOS.
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. atzichi@sc.itc.keio.ac.jp
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Ichihara
authors.forename: Matsuhiko
authors.initials: M
authors.lastname: Hayashi
authors.forename: Yukako
authors.initials: Y
authors.lastname: Koura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugaya
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Hirota
authors.forename: Takao
authors.initials: T
authors.lastname: Saruta
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D025461:Feedback, Physiological / Q000502:physiology*; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000098:blood supply / Q000502:physiology*; D007679:Kidney Medulla / Q000502:physiology / Q000601:surgery; D007684:Kidney Tubules / Q000098:blood supply / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018715:Microscopy, Video; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D010477:Perfusion / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014654:Vascular Patency / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D004791:Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; C496322:Nos1 protein, rat; D000086:Acetazolamide