Expression of endothelial nitric oxide synthase is suppressed in the renal vasculature of angiotensinogen-gene knockout mice.
We have attempted to elucidate the mechanism by which endothelial-type nitric oxide synthase (eNOS) is regulated in the kidney, with special reference to the role of renal hemodynamics and angiotensin II (Ang II). We compared angiotensinogen gene knockout (Atg-/-) mice, which lacked Ang II (resulting in sodium/water depletion and severe hypotension), with wild-type (Atg+/+) mice. Using Western blot analysis and the NADPH diaphorase histochemical reaction, we found that the expression and activity of eNOS were markedly lower in the renal vessels of Atg-/- mice compared with wild-type (Atg+/+) mice. Dietary salt loading significantly enhanced renal eNOS levels and increased blood pressure in Atg-/- mice, but severe hypotension almost abolished the effects of salt loading. In contrast, in Atg+/+ mice, altered salt intake or hydralazine had no effect on renal eNOS levels. These results suggest that perfusion pressure plays an essential role in maintaining renal vascular eNOS activity, whereas Ang II plays a supportive role, especially when renal circulation is impaired.
Kihara
Minoru
M
Department of Internal Medicine II, School of Medicine, Yokohama City University, Kanazawa-ku, Yokohama 236-0004, Japan. minoru@med.yokohama-cu.ac.j
Sato
Keiko
K
Hashimoto
Tatsuo
T
Imai
Nozomi
N
Toya
Yoshiyuki
Y
Umemura
Satoshi
S
D000804:Angiotensin II / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000201:enzymology*; D015153:Blotting, Western; D006830:Hydralazine / Q000494:pharmacology; D007022:Hypotension / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000098:blood supply* / Q000201:enzymology* / Q000503:physiopathology; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009252:NADPH Dehydrogenase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D012964:Sodium / Q000008:administration & dosage; D017673:Sodium Chloride, Dietary; D014882:Water-Electrolyte Balance / Q000235:genetics
D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; D006830:Hydralazine; D012964:Sodium; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D009252:NADPH Dehydrogenase