CONSTRICTION OF HUMAN DORSAL HAND VEINS INVIVO WITH SEVERAL VASOCONSTRICTORS AND THE INFLUENCE OF ORAL-ADMINISTRATION OF CARVEDILOL

In vivo measurements of human dorsal hand vein diameters have become a valuable tool in investigating vasoactive agents. This study in 13 healthy volunteers was performed to establish the influence of locally infused clonidine, angiotensin II, norepinephrine, and prostaglandin F2-alpha (PGF2-alpha) on hand vein diameter in a non-systemically active dose range. The study was intended to select agents suitable for venous preconstriction before and after oral administration of 50 mg carvedilol to obtain information on the mechanisms of vasodilation of this combined alpha- and beta-blocker. Infusions of norepinephrine (ED50, 20-40 ng/min) and PGF2-alpha (ED50, 480-1,170 ng/min) into the hand vein under investigation led to nearly complete constriction of the vessel. Infusions with clonidine and angiotensin II led to approximately 35% diameter reduction under the same conditions. A wide interindividual variety of hand vein dose response was observed for all vasoconstrictors. Oral administration of 50 mg carvedilol led to a rightward shift in the dose-response curves of angiotensin II, norepinephrine, and PGF2-alpha. On a 5% significance level, the venoconstrictive effects of norepinephrine and PGF2-alpha were attenuated by carvedilol compared with placebo. We conclude that a mechanism of vasodilation by carvedilol in addition to alpha-adrenoceptor antagonism could be responsible for the attenuation of venoconstriction induced by PGF2-alpha.