Pharmacological characterization of alpha(1)-adrenoceptor subtype mediating regulation of arterial pressure and urethral perfusion pressure in the anaesthetized rat

1 The alpha(1)-adrenoceptor subtypes mediating the regulation of arterial pressure (AP) and urethral perfusion pressure (UP) in the anaesthetized rat were characterized by using selective alpha(1)-adrenoceptor agonists and antagonists. 2 Intravenous administration of selective alpha(1)-adrenoceptor agonists elicited a dose-dependent increase in AP and UP. The rank order of agonist potency: oxymetazoline (ED(50), 6.2 and 8.2 nmol kg(-1)) > phenylephrine (ED(50), 32 and 27 nmol kg(-1)) > methoxamine (ED(50), 300 and 296 nmol kg(-1)) was the same for AP and UP, respectively. 3 The effects of phenylephrine on AP and UP were antagonized, in a dose related-manner, by pretreatment with alfuzosin, BMY 7378, 5-methyl-urapidil, phentolamine, prazosin, spiperone and WE 4101. S-methyl-urapidil was the only alpha(1)-adrenoceptor antagonist more potent on UP than on AP. 4 The potency of the different alpha(1)-adrenoceptor antagonists tested on AP and UP was significantly correlated with their binding affinity for the expressed recombinant alpha(1a)-, but not alpha(1b)- or alpha(1d)-, adrenoceptor subtype. 5 The results suggest that in the anaesthetized rat (1) both AP and UP are regulated by the alpha(1A)-adrenoceptor subtype; and (2) the urogenital selectivity of 5-methyl-urapidil may be due to the existence of multiple forms of the alpha(1A)-adrenoceptor.