Endothelin receptor A blockade alters hemodynamic response to nitric oxide inhibition in rats.
We examined the extent to which the systemic and renal vasoconstriction induced by nitric oxide (NO) inhibition in vivo is mediated by endothelin (ET). We examined the effects of BQ-610, a specific ETA-receptor antagonist, after NO inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) in the anesthetized rat. Mean arterial pressure (MAP) increased after L-NAME infusion from 107 +/- 2 to 133 +/- 3 mmHg (P < 0.05 vs. baseline period) then fell to 115 +/- 3 mmHg after administration of BQ-610 (P < 0.05 vs. L-NAME and baseline periods). Systemic vascular resistance (SVR) increased from 1.26 +/- 0.06 to 2.17 +/- 0.18 mmHg.ml-1.min.300 g after L-NAME (P < 0.05 vs. baseline period) then fell to 1.69 +/- 0.12 mmHg.ml-1.min.300 g after BQ-610 (P < 0.05 vs. L-NAME and baseline periods). The increase in renal vascular resistance (RVR) from 6.4 +/- 0.4 to 13.7 +/- 1.4 mmHg.ml-1.min.300 g induced by L-NAME (P < 0.05 vs. baseline period) was reduced to 11.1 +/- 1.0 mmHg.ml-1.min.300 g by BQ-610 (P < 0.05 vs. L-NAME and baseline periods). The extent to which BQ-610 reversed the L-NAME-induced increases in RVR and SVR was comparable (RVR by 40 +/- 9%; SVR by 52 +/- 7%). Glomerular filtration rate and renal blood flow were both reduced by L-NAME, but neither value increased after BQ-610, possibly because the renal vasodilation induced by ETA blockade was offset by the concomitant reduction in MAP and renal perfusion pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Thompson
A
A
Evans Memorial Department of Clinical Research, Boston University Medical Center, Massachusetts 02118, USA.
Valeri
C R
CR
Lieberthal
W
W
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D009842:Oligopeptides; C087220:BQ 610; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester