SR141716A-Sensitive Enhancement of ET-1 Hypotensive Effect by Chronic NOS Inhibition

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2003-10, Vol.42 (4, Part 2), p.802-805
• Main Authors: Souza, Hugo C.D, Salgado, Helio C, Ballejo, Gustavo, Salgado, Maria Cristina O
• Format: Article
• Language: English
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Cardiology. Vascular system; Drug Synergism; Endothelin-1 - pharmacology; Enzyme Inhibitors - pharmacology; Experimental diseases; Heart Rate - drug effects; Hypertension - chemically induced; Hypertension - physiopathology; Male; Medical sciences; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Rats; Rats, Wistar; Receptors, Cannabinoid; Receptors, Drug - antagonists & inhibitors; Vasodilator Agents - pharmacology
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.0000088362.50484.4C

ABSTRACT—The present study evaluated the potential mechanism involved in the hypotensive effect induced by ET-1 in rats treated with the NO synthase inhibitor N-nitro-l-arginine methyl ester (L-NAME) in the drinking water during 7 days. Hypertension developed in the L-NAME–treated rats (164±3 versus 112±1 mm Hg in untreated control rats), and the hypotensive effect of ET-1 (100 pmol/kg IV) was significantly enhanced compared with control rats (32±2% versus 20±1% fall in mean arterial pressure). The enhanced ET-1 hypotensive effect in L-NAME–treated rats was abolished by the ETB receptor antagonist BQ-788 but was unaltered by the cyclooxygenase inhibitor diclofenac, the cytochrome P450 inhibitor fluconazole, or the potassium channel blockers apamin, glibenclamide, tetraethylammonium, and 4-aminopyridine. Pretreatment with the cannabinoid CB1 receptor antagonist SR141716A significantly reduced the hypotensive response to ET-1 in L-NAME–treated rats (20±1%), although it did not modify the response in untreated control rats (17±1%). These findings indicate that in rats under chronic NOS inhibition, the hypotensive effect of ET-1 is unexpectedly enhanced and appears to be mediated by a non-NO/non-prostanoid mechanism and involves an SR141716A-sensitive mechanism triggered by ETB receptor activation.