rs-100329 and Hypertension--Renovascular

We investigated the effect of inter-renal aortic coarctation on the function and expression of vascular α(1A)- and α(1D)-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 (α(1A)- and α(1D)-adrenoceptor in aorta and caudal arteries), and immunoassay (plasma ATII). The α(1D)-adrenoceptor antagonist, BMY-7378 (BMY) blocked noradrenaline-induced responses in the order SO > AC7 ≫ AC14; in contrast, the α(1A)-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 α(1A)-adrenoceptor agonist A-61603 increased in rats with AC14, and responses were inhibited by RS in the order AC14 > AC7 > SO. In aorta, α(1D)-adrenoceptor protein increased in AC7 and decreased in AC14; α(1A)-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 α(1D)-adrenoreceptors in the development of hypertension in this experimental model.

Topics: Adrenergic alpha-1 Receptor Agonists; Adrenergic alpha-1 Receptor Antagonists; Angiotensin II; Animals; Aorta; Aortic Coarctation; Dose-Response Relationship, Drug; Hypertension, Renovascular; Imidazoles; Male; Norepinephrine; Piperazines; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-1; Tetrahydronaphthalenes; Thymine