Alpha-adrenoceptor blocking action of terazosin

alpha-Adrenoceptor blocking activities and vascular relaxation activities of terazosin, a new antihypertensive agent, were studied. Terazosin had no effect on Ba2+, serotonin, angiotensin II and Ca2+ induced contractions in the isolated rat aorta. Terazosin competitively inhibited norepinephrine (NE) and phenylephrine (PE) induced contractions of the isolated rat aorta, and their pA2 values were 9.28 and 8.74, respectively. The potency of terazosin in the NE induced contraction was about 0.11, 8 and 176 times more than prazosin, phentolamine and yohimbine, respectively. The potency of terazosin in the PE induced contraction was about 0.09, 6 and 60 times more than prazosin, phentolamine and yohimbine. Terazosin (i.v.) competitively inhibited the PE induced pressor response. The "pA2" values of postsynaptic alpha-adrenoceptor blocking activity was 5.22, and its potency was about 0.05, 5 and 62.5 times more than prazosin, phentolamine and yohimbine, respectively. Terazosin (0.3 mg/kg, i.v. or less) did not show any significant effect on clonidine induced bradycardia during electrical stimulation of cardiac sympathetic nerve, whereas prazosin (0.3 mg/kg), phentolamine (0.1 mg/kg) and yohimbine (0.1 mg/kg) antagonized the effect of clonidine by 37%, 80.6% and 63.3%, respectively. Terazosin, 0.3 and 1 mg/kg, p.o., antagonized the PE (3 micrograms/kg, i.v.) induced pressor response in conscious unrestrained rats. This effect lasted for 8 hr in the case of 0.3 mg/kg and lasted for 12 hr in the case of 1 mg/kg. Thus, it is strong suggested that the antihypertensive effect of terazosin is based on the postsynaptic alpha-adrenoceptor blocking action.