Alpha-2 adrenoceptor subtype causing nitric oxide-mediated vascular relaxation in rats

Charles Bockman, Isabel Gonzalez-Cabrera, Peter W. Abel

Research output: Contribution to journalArticle

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Abstract

The alpha-2 adrenoceptor subtype and its signal transduction pathway mediating vascular relaxation in rats were studied in vitro using rings of superior mesenteric arteries. Removal of endothelium or incubation with N(G)- nitro-L-arginine completely blocked relaxant responses to UK14,304, suggesting endothelium-derived nitric oxide mediates relaxation. The order of potency for full (F) or partial (P) agonists causing relaxation was guanabenz (P) > UK14,304 (F) > clonidine (P) > epinephrine (F) > norepinephrine (F). Affinities (K(B)) of alpha-2 adrenoceptor subtype-selective drugs for blocking relaxation were obtained in side-by-side experiments comparing rat mesenteric arteries with pig coronary arteries. Relaxation of pig coronary arteries is known to be mediated by the alpha-2A adrenoceptor subtype. K(B) values in nM for rauwolscine (19), WB-4101 (265), SKF-104078 (197), spiroxatrine (128), and prazosin (1531) for blocking relaxation in rat arteries were consistent with their affinities for binding at the alpha-2D adrenoceptor subtype. K(B) values for rauwolscine and WB-4101, drugs distinguishing the alpha-2D from the alpha-2A adrenoceptor subtype, were significantly higher in blocking relaxation of rat arteries compared with pig arteries, suggesting the alpha-2D adrenoceptor subtype mediates NO-induced relaxation in rat arteries. We used forskolin to oppose alpha-2 adrenoceptor- mediated inhibition of cAMP formation by directly stimulating cAMP formation in endothelium. Forskolin did not affect the relaxant response to UK14,304, suggesting that cAMP is not involved in the coupling of alpha-2 adrenoceptors to nitric oxide-induced vascular relaxation.

Original languageEnglish
Pages (from-to)1235-1243
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume278
Issue number3
StatePublished - Sep 1996

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Adrenergic Receptors
Blood Vessels
Nitric Oxide
Arteries
spiroxatrine
Swine
Yohimbine
Colforsin
Endothelium
Coronary Vessels
Guanabenz
Mesenteric Arteries
Superior Mesenteric Artery
Prazosin
Clonidine
Pharmaceutical Preparations
Epinephrine
Arginine
Signal Transduction
Norepinephrine

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Alpha-2 adrenoceptor subtype causing nitric oxide-mediated vascular relaxation in rats. / Bockman, Charles; Gonzalez-Cabrera, Isabel; Abel, Peter W.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 278, No. 3, 09.1996, p. 1235-1243.

Research output: Contribution to journalArticle

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