In vitro relaxation of arteries and veins by prazosin: alpha-adrenergic blockade with no direct vasodilation.
Controversy exists regarding the mechanism by which prazosin lowers blood pressure without a marked increase in heart rate; a mechanism involving both sympatholytic activity and direct smooth muscle relaxation has been suggested. alpha-Adrenergic receptor blockade by prazosin is well documented and occurred to exogenous norepinephrine and to field stimulation in vitro in rat arteries and veins. A parallel shift of the norepinephrine concentration response curves in the aorta and mesenteric artery contrasted with a nonparallel shift and a marked depression of maximal norepinephrine responses in the inferior vena cava, portal, iliac and femoral veins. Nonspecific direct acting vasodilators will antagonize contractile responses to all agonists. However, prazosin (10(-8) M) specifically antagonized norepinephrine-induced responses. Concentration response curves to potassium chloride or to serotonin were not affected in these rat tissues. In addition, prazosin (up to 10(-6) M) did not significantly relax aortic tissue previously contracted with potassium chloride or serotonin, whereas the vasodilator, nitroglycerin, produced a clear relaxation. Prazosin only reduced the tone of vessels contracted with norepinephrine. These data indicate that prazosin exhibits minimal, if any, direct smooth muscle relaxant properties in concentrations higher than those producing alpha-adrenergic receptor blockade, and relaxes rat veins by a mechanism involving alpha-adrenergic receptor blockade.
D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000294:innervation; D004558:Electric Stimulation; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014680:Veins / Q000187:drug effects* / Q000294:innervation
D011799:Quinazolines; D011942:Receptors, Adrenergic, alpha; D012701:Serotonin; D005996:Nitroglycerin; D009638:Norepinephrine; D011224:Prazosin; D010646:Phentolamine