alpha_(1A)-adrenergic receptor mediated pressor response to phenylephrine in anesthetized rat

摘要

To determine which subtype of a_1-adrenergic receptors plays a role in the regulation of blood pressure, with alpha_(1A)-adrenergic receptor-mediated vasoconstriction in perfused hindlimb as a control, we compared the inhibitory effects of various alpha_1-adrenergic receptor selective antagonists on the vasopressure responses to phenylephrine between the mean arterial pressure and hindlimb perfusion pressure in anesthetized rats. In Normotensive Wistar rats, the results showed that the inhibitory effects (dose ratios of ED_(50), Dr) of aradrenoceptor selective antagonist {prazosin, Dr 13.5 ± 3.6 vs.15.1 ± 4.3, n = 11), alpha_(1A)-adrenoceptor selective antagonist (5-methyl-urapidil, Dr 2.4 ± 0.9 vs. 3.7 ± 2.3, n= 12; RS-17053, Dr 3.2 ± 1.6 vs.4.4 ± 3.3, n=12) and alpha_(1D)- adrenoceptor selective antagonist (BMY7378, Dr 1.9 ± 0.9 vs. 2.2 ±0.8, n = 8) on phenylephrine- induced increases of perfusion pressure in the autoperfused femoral beds were the same as that in the mean arterial bloodpressure in normotensive Wistar rats. The inhibitory effects of antagonists (RS-17053, Dr 3.4 ± 0.6 vs. 4.3 ± 0.9, n = 5; BMY7378, Dr 1.7±0.5 vs. 1.7 ± 0.5, n = 8) in spontaneous hypertensive rats were similar with the Wistar rats. These results suggest that the mean arterial pressure induced by phenylephrine was mainly mediated by aiA-adrenergic receptor in both the anesthetized Wistar rats and spontaneous hypertensive rats.