Contribution of endothelin to the acute pressor response of L-NAME in stroke-prone spontaneously hypertensive rats

Journal of Cardiovascular Pharmacology
J FinkC T Stier

Abstract

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-...Continue Reading

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Citations

Jun 28, 2000·Journal of the Autonomic Nervous System·P M Vanhoutte
Feb 2, 2000·Current Opinion in Nephrology and Hypertension·C Chatziantoniou, J C Dussaule
Sep 9, 2011·Journal of Comparative Pathology·A S FelixJ J de Carvalho
Apr 22, 2014·Life Sciences·Jo G R De Mey, Paul M Vanhoutte
Jul 13, 2012·American Journal of Hypertension·Nilka de Jesus-GonzalezBenjamin D Humphreys
Aug 16, 2013·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Ji Hoon SungSang Soo Sim
Aug 18, 2006·Journal of Hypertension·Ahmad BlantonAdebayo Oyekan
Aug 31, 1999·Journal of Hypertension·P M Vanhoutte
Jul 1, 2020·Endocrine, Metabolic & Immune Disorders Drug Targets·Fadwa El-Ouady, Mohamed Eddouks

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