Journal article
β-Adrenoceptor Dysfunction After Inhibition of NO Synthesis
Hypertension (Dallas, Tex. 1979), Vol.36(3), pp.376-382
09/2000
DOI: 10.1161/01.HYP.36.3.376
PMID: 10988268
Abstract
Abstract —G s protein–coupled β-adrenoceptors rapidly desensitize on exposure to agonists in reconstituted membrane preparations, whereas rapid tachyphylaxis to β-adrenoceptor–mediated vasodilation does not readily occur in vivo. This study examined the possibility that endothelium-derived nitrosyl factors prevent the rapid desensitization of β-adrenoceptors in the vascular smooth muscle of resistance arteries in pentobarbital-anesthetized rats. The fall in mean arterial blood pressure and in hindquarter vascular resistance produced by the β-adrenoceptor agonist isoproterenol (ISO, 0.1 to 10 μg/kg IV) was slightly but significantly smaller in rats treated with the NO synthase inhibitor N G -nitro- l -arginine methyl ester (L-NAME, 100 μmol/kg IV) than in saline-treated rats. The ISO-induced fall in mesenteric resistance was similar in L-NAME–treated and in saline-treated rats. The fall in hindquarter vascular resistance and in mesenteric resistance produced by ISO (8×10 μg/kg IV) was subject to tachyphylaxis on repeated injection in rats treated with L-NAME (100 μmol/kg IV) but not in rats treated with saline. Injections of l - S -nitrosocysteine (1200 nmol/kg IV), a lipophobic S -nitrosothiol, before each injection of ISO (10 μg/kg IV) prevented tachyphylaxis to ISO in L-NAME–treated rats. The vasodilator effects of ISO (0.1 to 10 μg/kg IV) in L-NAME–treated rats that received 8 injections of ISO (10 μg/kg IV) were markedly smaller than in L-NAME–treated rats that received 8 injections of saline. These results indicate that (1) the vasodilator actions of ISO in pentobarbital-anesthetized rats only minimally involve the release of endothelium-derived nitrosyl factors, (2) the effects of ISO are subject to development of tachyphylaxis in L-NAME–treated rats, and (3) tachyphylaxis to ISO is prevented by l - S -nitrosocysteine. These findings suggest that endothelium-derived nitrosyl factors may prevent desensitization of β-adrenoceptors in vivo.
Details
- Title: Subtitle
- β-Adrenoceptor Dysfunction After Inhibition of NO Synthesis
- Creators
- Erin J Whalen - From the Departments of Pharmacology (E.J.W., A.K.J., S.J.L.) and Psychology (A.K.J.) and The Cardiovascular Center (E.J.W., A.K.J.), University of Iowa, Iowa CityAlan Kim Johnson - From the Departments of Pharmacology (E.J.W., A.K.J., S.J.L.) and Psychology (A.K.J.) and The Cardiovascular Center (E.J.W., A.K.J.), University of Iowa, Iowa CityStephen J Lewis - From the Departments of Pharmacology (E.J.W., A.K.J., S.J.L.) and Psychology (A.K.J.) and The Cardiovascular Center (E.J.W., A.K.J.), University of Iowa, Iowa City
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.36(3), pp.376-382
- DOI
- 10.1161/01.HYP.36.3.376
- PMID
- 10988268
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 09/2000
- Academic Unit
- Psychological and Brain Sciences; Neuroscience and Pharmacology; Health and Human Physiology
- Record Identifier
- 9984213411602771
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