alpha-Adrenoceptor subtypes in cardiovascular regulation.

A great deal of experimental observations at alpha-adrenoceptors may be explained if two points are considered: (1) the alpha 1-/adrenoceptor ratio (selectivity ratio) of a given drug and (2) the ratio of alpha 1-/adrenoceptors in the target organ or tissue. The alpha 1-/alpha 2-selectivity ratio for 10 agonists was determined in pithed rats by their hypertensive effect in the presence or absence of the antagonists rauwolscine or prazosin, respectively. Treatment with a beta-blocking agent made it possible to test drugs with additional beta-adrenergic potencies (phenylethylamines). Methoxamine exerted the highest alpha 1-/alpha 2-selectivity ratio, the azepine derivative B-HT 920 the lowest ratio, i.e., the highest selectivity for alpha 2-adrenoceptors. Using the two selective agonists methoxamine and B-HT 920, respectively, the alpha 1-/alpha 2-adrenoceptor ratio (importance) in several target systems was estimated (determination of equieffective doses). Results indicated the prevalence of alpha 1-adrenoceptors in the nictitating membrane, and the equal importance of both subtypes at peripheral postsynaptic vascular sites in rats, as well as in cats. At presynaptic sites (cardiac nerve, rats), alpha 2-adrenoceptors are prevalent. A comparison of equieffective doses of B-HT 920 and clonidine in cats indicated the alpha 2-nature of the central adrenoceptors which mediate hypotension.