Does segmental difference in α1-adrenoceptor subtype explain contractile difference in rat abdominal and thoracic aortae?

The cyclooxygenase inhibitor, indomethacin, depresses adrenergic agonist constriction of endothelium-denuded rat abdominal, but not thoracic, aorta. In order to explain this finding, we explored the possibility of segmental differences in the population of alpha(1)-adrenoceptor (AR) subtypes. In endothelium-denuded tissues, phenylephrine elicited concentration-dependent contractions in the thoracic and abdominal aortic rings with potencies and maximal effects that, respectively, did not differ significantly (P>.05). Indomethacin (1 x 10(-5) M) inhibited phenylephrine-induced contractions only in abdominal aorta. The subtype-selective alpha(1D)-AR antagonist, BMY 7378, was found to antagonize contractions to phenylephrine competitively in abdominal (pA(2) 8.44) and thoracic (pA(2) 8.56) aortic rings. These data are consistent with published alpha(1D)-AR functional potency and clonal alpha(1D)-AR binding affinity. In addition, cumulative concentration-contraction curves for phenylephrine were competitively antagonized in the rat abdominal and thoracic aortae by prazosin, 5-methylurapidil and WB 4101, with pA(2) values of 9.39 and 9.61, 7.64 and 7.85, and 9.43 and 9.58, respectively. These compounds with varying degrees of subtype selectivity inhibited contractions of the thoracic and abdominal aortae with affinities consistent with those determined at the alpha(1D)-AR subtype. The results of this study suggest that the contraction to phenylephrine of the rat abdominal and thoracic aorta is mediated via the same alpha(1D)-AR subtype. (C) 2002 Elsevier Science Inc. All rights reserved.