alpha1A-adrenergic receptor mediated pressor response to phenylephrine in anesthetized rat.

To determine which subtype of alpha1-adrenergic receptors plays a role in the regulation of blood pressure, with alpha1A-adrenergic receptor-mediated vasoconstriction in perfused hindlimb as a control, we compared the inhibitory effects of various alpha1-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 ED50, Dr) of alpha1-adrenoceptor selective antagonist (prazosin, Dr 13.5+/-3.6 vs.15.1+/-4.3, n = 11), alpha1A-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 alpha1D-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 blood pressure 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 alpha1A-adrenergic receptor in both the anesthetized Wistar rats and spontaneous hypertensive rats.