| Abstrakt: |
To evaluate the hypothesis of a-antagonism as a contributing factor to the vascular action of calcium entry blockade (CEB) in man, we have compared the action of verapamil, a CEB, on nonselective (norepinephrine, NE) and selective a1- (methoxamine, MET) and a2- (B-HT 933, BHT) adrenergic agonists in human forearm vasculature. All drugs were infused into the brachial artery at systemically ineffective rates. Blood pressure and heart rate were continuously monitored; forearm blood flow was measured through strain gauge plethysmography. Sixteen mild, untreated hypertensive patients were studied. Cumulative forearm blood flow dose-response curves to three cumulative infusion rates (3 min each) of NE (0.015, 0.05, 0.15 µg/100 ml tissue/min), MET (0.06, 0.6, 6 µg/100 ml tissue), and BHT (3, 10, 30 µg/100 ml tissue/min) were obtained during saline and after verapamil (0.9 µg/100 ml tissue/min ± 15 min) infusion. Verapamil did not modify to any significant extent NE-mediated vasoconstriction, but clearly blunted the vascular action of either MET or BHT. Because NE is the physiological neurotransmitter, the data cast doubts about the relevance of a-antagonism as a mechanism of action of calcium entry blockade through verapamil. Besides, the data caution against generalizing by using data obtained through several compounds, including CEBs, of a-adrenergic stimuli. |
