Contribution of endothelin to the acute pressor response of L-NAME in stroke-prone spontaneously hypertensive rats.
In this study, we examined whether endothelin (ET) plays a role in the short-term increase in mean arterial pressure (MAP) after nitric oxide synthase (NOS) inhibition with N(omega)-nitro-L-arginine methyl ester (L-NAME) in stroke-prone spontaneously hypertensive rats (SHRSPs). Experiments were performed by using Inactin-anesthetized male SHRSPs that were pretreated with chlorisondamine to block reflex autonomic cardiovascular effects. Injection of L-NAME (10 mg/kg, i.v.), but not D-NAME, produced rapid and marked increases (74 +/- 3 mm Hg) in MAP that were sustained for >1 h. In SHRSPs that were treated with the ET(A/B) receptor antagonist, L-754,142 (15 mg/kg + 15 mg/kg/h), L-NAME increased MAP by 45 +/- 4 mm Hg (p < 0.0001 compared with L-NAME alone). L-754,142 blocked pressor responses to big ET-1 by >90% but was without effect on pressor responses to norepinephrine. Plasma levels of ET-1 averaged 5 +/- 1 pg/ml in animals given vehicle and were slightly increased in animals given either L-NAME alone (7 +/- 2 pg/ml) or L-754,142 alone (7 +/- 2 pg/ml) but increased markedly when L-NAME and L-754,142 were given together (114 +/- 18 pg/ml). This may relate to an effect of L-754,142 to block ET-receptor-mediated clearance of ET-1. We conclude that ET plays a role in the short-term pressor response after NOS inhibition in SHRSPs.
Fink
J
J
Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
Fan
N Y
NY
Rosenfeld
L
L
Stier
C T
CT
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002561:Cerebrovascular Disorders / Q000209:etiology; D002714:Chlorisondamine / Q000494:pharmacology; D004357:Drug Synergism; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D011918:Rats, Inbred SHR
D000081:Acetamides; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; C097296:L 754142; D019001:Nitric Oxide Synthase; D002714:Chlorisondamine; D019331:NG-Nitroarginine Methyl Ester