Renal nitric oxide and angiotensin II interaction in renovascular hypertension.
In two-kidney, one clip (2K1C) renovascular hypertension, blood flow is reduced to the clipped but not to the nonclipped kidney, despite elevated angiotensin II. To determine possible interactions between endothelium-derived nitric oxide and angiotensin, we studied bilateral renal blood flow using radioactive microspheres in anesthetized 2K1C hypertensive rats 4 weeks after clipping. We studied the response to nitric oxide synthesis inhibition with 10 mg/kg body wt NG-nitro-L-arginine- methyl ester (L-NAME) in hypertensive rats untreated (n = 5) or treated (n = 5) with 10 mg/kg body wt of the angiotensin II antagonist losartan. 2K1C rats had a blood pressure of 159 +/- 9 mm Hg, and renal blood flow to the clipped kidney was reduced 87% compared with the nonclipped kidney. L-NAME increased blood pressure 36 +/- 5 mm Hg and decreased renal blood flow in the nonclipped kidney 61% (4.9 +/- 0.5 to 1.9 +/- 0.4 mL/min per gram kidney weight, P < .001). Renal vascular resistance increased 200% (33.4 +/- 2.2 to 100.7 +/- 15.0 resistance units [RU], P < .005). Renal blood flow and resistance in the clipped kidney were unchanged by L-NAME. Treatment of 2K1C rats with losartan reduced blood pressure (154 +/- 8 to 116 +/- 11 mm Hg, P < .01), did not change blood flow in the nonclipped, but normalized it in the clipped kidney (4.8 +/- 0.8 mL/min per gram kidney weight).(ABSTRACT TRUNCATED AT 250 WORDS)
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Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Mich. 48202-2689.
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D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D019808:Losartan; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D009569:Nitric Oxide; D001120:Arginine; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester