Renal versus femoral hemodynamic response to endothelium-derived relaxing factor synthesis inhibition.
Systemic inhibition of endothelium-derived relaxing factor (EDRF) synthesis leads to acute hypertension and increased peripheral vascular resistance. The changes in vascular resistance are not evenly distributed to all vascular beds. In this study, we compared the renal and femoral hemodynamic responses to EDRF synthesis inhibition. Renal blood flow (RBF) and femoral blood flow (FBF) were assessed in the presence and absence of DuP 753, an angiotensin II receptor antagonist. Inhibition of EDRF synthesis by a bolus dose of Lw-nitroarginine methyl ester (L-NAME) increased blood pressure (BP) by 21 +/- 1 mm Hg (p < 0.001) and decreased RBF by 32 +/- 5% (from 5.9 +/- 0.5 to 3.9 +/- 0.3 ml/min/g kidney weight; p < 0.005) while FBF remained unchanged (9.5 +/- 0.4 versus 9.4 +/- 0.4 ml/min). Renal vascular resistance (RVR) increased by 83 +/- 16% (p < 0.001), compared with only a 24 +/- 6% increase in femoral vascular resistance (FVR; p < 0.005). To eliminate the influence of systemic hypertension, we returned organ perfusion pressure to pre-L-NAME levels by partial aortic constriction. The kidney maintained RBF by decreasing RVR by 8 +/- 2% (p < 0.02), while FBF decreased by 15 +/- 5% (p < 0.01). When rats were pretreated with DuP 753, L-NAME still increased BP by 22 +/- 2 mm Hg, but RVR increased by only 26 +/- 5% (from 13.2 +/- 1.6 to 16.8 +/- 2.7; p < 0.01) and RBF did not change. DuP 753 had no effect on the femoral vascular response to L-NAME.(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 / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005269:Femur / Q000098:blood supply*; D006439:Hemodynamics; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation; D013777:Tetrazoles / Q000494:pharmacology
D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D009569:Nitric Oxide; D001120:Arginine; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester