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.
D000317:Adrenergic alpha-Antagonists; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D011224:Prazosin / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D011799:Quinazolines; D000804:Angiotensin II; D009638:Norepinephrine; D011224:Prazosin