<i>In vitro </i>Relaxation of Arteries and Veins by Prazosin: Alpha-Adrenergic Blockade with No Direct Vasodilation

Abstract

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. α-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^–6M) 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 α-adrenergic receptor blockade, and relaxes rat veins by a mechanism involving α-adrenergic receptor blockade.

Non‐competitive antagonism of the α‐adrenoceptor‐mediated fast component of contraction of rat aorta, by doxazosin and prazosin

“…Cohen, Wiley & Slater (1979) demonstrated a competitive blockade of NA-induced contractions by prazosin in rat isolated aorta. These investigators used cumulative DRCs in which the fast component of contraction cannot be separately assessed.…”

Hyperreactivity of coronary arterial smooth muscles in response to ergonovine from rabbits with hereditary hyperlipidemia.

“…The mechanism of ergonovine-induced contractions of rabbit arteries was defined by the use of specific antagonists. Prazosin was chosen as the competitive a-adrenergic antagonist, since it had negligible serotonergic receptor antagonist activity (Doxey et al, 1977;Cohen et al, 1979). The antagonist activity of cyproheptadine, a drug classified as a serotonergic antagonist (Apperley et al, 1976(Apperley et al, , 1980, was examined in the four different types of arteries.…”

“…Accordingly, the reactivity of carotid and femoral arteries from WHHL rabbits to the vasoconstrictor effects of ergonovine was not altered, in contrast to the response of coronary artery and aorta. The concentration-response relations for serotonin and phenylephrine in the carotid and femoral arteries demonstrate that vascular reactivities to these agonists were similar with respect to threshold Table Z adrenergic receptor, since it had repeatedly been shown to have negligible serotonergic antagonistic activity (Doxey et al, 1977;Cohen et al, 1979). Cyproheptadine was used as a blocking agent of the serotonergic receptor (Apperley et al, 1976(Apperley et al, , 1980.…”

Modulation of noradrenergic transmission in the guinea‐pig mesenteric artery: an electrophysiological study.

“…Therefore, these receptors have been classified into a2 and xc, respectively (Starke & Endo, 1976;Starke, 1977;Langer, 1977; McCulloch & Story, 1980;Bevan, 1980). However, the a2-adrenoceptors are not distributed only on prejunctional nerve terminals, because in various veins prazosin does not act as a competitive antagonist of the contractile response to NA, whereas yohimbine is more effective on the post-junctional adrenoceptors as a competitive antagonist than it is in the arteries (Cohen, Wiley & Slater, 1979). Furthermore, the post-junctional a-adrenoceptors distributed on smooth muscles of the guinea-pig mesenteric arteriole and saphenous artery differed in nature from a,-and a2-adrenoceptors.…”