ISSN:
1432-1440
Keywords:
Carvedilol
;
Prazosin
;
Hand vein
;
Receptor binding
;
Vasoconstriction
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Carvedilol is a β-blocker with additional vasodilating activity. This study was performed in order to determine whether the vasodilator action of orally administered carvedilol in man is based upon an α-adrenoceptor antagonism exclusively or if evidence for an additional mechanism could be confirmed. The influence of carvedilol (50 mg p.o.) and prazosin (2 mg p.o.) upon the vasoconstrictor effect of noradrenaline and prostaglandin F2α, infused into superficial hand veins, was established in 8 healthy male volunteers. Increasing dosages of the vasoconstrictors below their threshold of systemic activity were employed in order to obtain dose-response curves of the hand veins congested at a venous occlusion pressure of 40 mmHg. These dose-response curves were repeated 1 and 3.5 h after oral administration of either carvedilol, prazosin, or placebo. The ex vivo, in vitro α1-receptor occupancy in plasma was measured before and after each vasoconstrictor dose-response curve, using an α1-radioreceptor binding assay. Washout periods of 48 h were kept between study days, investigating the influence of one orally administered drug upon one of the local vasoconstrictor dose-response curves at a time. In the α1-radioreceptor assay, plasma concentrations from 0.9- to 1.7-fold the equilibrium dissociation constant (K i) of carvedilol could be evaluated 1 as well as 3.5 h after medication, corresponding with a receptor occupancy of 44%–63%. After prazosin, 9–13 times the K i values were determined, which amounts to an α1-adrenoceptor occupation of about 90%–93%. Consequently, the dose-response curves to noradrenaline of the hand veins were attenuated to a greater extent after oral prazosin compared with carvedilol. In contrast, no statistically significant differences between the effects of carvedilol and prazosin could be found as regards the vasoconstriction induced by prostaglandin F2α. An oral placebo did not affect the reproducibility of either vasoconstrictor dose-response curve. We conclude that the relatively weak occupancy at α1-receptors by carvedilol cannot fully explain the effectivity of carvedilol (50 mg p.o.) in inhibiting prostaglandin F2α-induced vasoconstriction when compared with prazosin (2 mg p.o.). An additional mechanism of vasodilation could be responsible for this phenomenon
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00207606
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