Renal effects of acute endothelial-derived relaxing factor blockade are not mediated by angiotensin II.
The renal responses to acute blockade of the endothelial-derived relaxing factor (EDRF) resemble the renal actions of angiotensin II (ANG II), and the present studies were conducted to establish what role, if any, the endogenous renin-angiotensin system plays in mediating the renal response to acute EDRF blockade. These studies were conducted in the conscious chronically catheterized rat. In control experiments we observed that acute blockade of ANG II synthesis with converting-enzyme inhibition (CEI) led to a fall in blood pressure (BP) and a slight renal vasodilation but no significant change in glomerular filtration rate (GFR) or renal plasma flow (RPF). Urine flow and sodium excretion were unchanged by CEI. Use of the nonpeptide ANG II receptor antagonist losartan had no effect on BP, renal vascular resistance (RVR), GFR, or RPF; however, urine flow and sodium excretion did rise significantly. Because of the high specificity of losartan, this suggests that, in the normal conscious rat, endogenous ANG II does not control renal vascular tone but does enhance renal sodium reabsorption. ANG II blockade with either CEI or losartan had little effect on BP and no effect on the renal hemodynamic responses to acute EDRF blockade. The marked natriuretic and diuretic response to acute EDRF blockade persists during concomitant losartan but is abolished by CEI. These studies suggest that in the conscious rat the renal hemodynamic response to EDRF blockade is not mediated by endogenous ANG II.
Baylis
C
C
Department of Physiology, West Virginia University, Morgantown.
Engels
K
K
Samsell
L
L
Harton
P
P
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D019808:Losartan; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009318:Natriuresis / Q000187:drug effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D009569:Nitric Oxide; D001120:Arginine; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester