Relationship between the hypotensive and alpha-adrenoceptor blocking actions of prazosin

The relationship between the hypotensive and alpha-adrenoceptor blocking actions of prazosin was investigated in anaesthetized rats. Pressor responses to norepinephrine and angiotensin II were determined before and after intravenous administration of prazosin, 0.0005 to 0.7 mg/kg. The prazosin-induced reduction in mean arterial pressure was recorded immediately before measurement of 87 such pairs of pressor reponses. The percentage antagonism of norepinephrine-induced pressor responsivity, corrected where necessary for non-specific changes in pressor sensitivity, was used as an index of alpha-adrenoceptor blockade. Linear regression analysis of the data revealed that there was a highly significant correlation between the degree of alpha-adrenoceptor blockade afforded by prazosin and the hypotensive response to the drug. The findings extend those of previous studies in which alpha-blocking properties of prazosin were demonstrated using doses of the drug 10(2) to 10(4)-fold greater than those producing significant hypotensive effects. The present results show that prazosin exhibits alpha-adrenoceptor blocking properties at much lower doses, such that a close relationship exists between its alpha-blocking activity and its hypotensive effects.