Effect of inter-renal aortic coarctation-induced hypertension on function and expression of vascular α1A- and α1D-adrenoceptors

Abstract

We investigated the effect of inter-renal aortic coarctation on the function and expression of vascular a1A- and a1D-adrenoceptors and plasma angiotensin II (ATII) in rats. Male Wistar rats, either sham operated (SO), or with aortic coarctation for 7 (AC7) and 14 days (AC14) were used for agonist-induced pressor responses in vehicle (physiological saline)- and antagonist-treated anesthetized animals, immunoblot analysis (α1A- and α1D-adrenoceptor in aorta and caudal arteries), and immunoassay (plasma ATII). The a1D-adrenoceptor antagonist, BMY-7378 (BMY) blocked noradrenalineinduced responses in the order SO > AC7 ≫ AC14; in contrast, the α1A-adrenoceptor antagonist RS-100329 (RS), produced a marginal shift to the right of the dose-response curve to noradrenaline, along with a strong decrease of the maximum pressor effect in the order SO > AC7 = AC14. The potency of the α1A-adrenoceptor agonist A-61603 increased in rats with AC14, and responses were inhibited by RS in the order AC14 > AC7 > SO. In aorta, α1D-adrenoceptor protein increased in AC7 and decreased in AC14; α1A-adrenoreceptor protein increased in the caudal artery of AC7 and returned to control values in AC14. Plasma ATII increased in AC7 and AC14, compared with SO rats. These results suggest an early and direct relationship between ATII and a1D-adrenoreceptors in the development of hypertension in this experimental model.