Effects of calcium channel blockers on the contractile response to dihydroergotamine in isolated human femoral veins.

Contractions induced in spirally cut human postmortem femoral veins by dihydroergotamine, noradrenaline, or 5-hydroxytryptamine (5-HT) were measured isometrically. The influence of calcium channel blockers (verapamil, diltiazem and nifedipine), lanthanum chloride and withdrawal of external calcium on the contractile response of veins to dihydroergotamine was investigated. The agonists noradrenaline and 5-HT were studied in comparison. Verapamil and nifedipine up to a concentration of 1 mumol/l caused a shift to the right of the cumulative concentration-response curves for noradrenaline and 5-HT with a reduction of the maximum contraction. Diltiazem affected the contractile response to 5-HT slightly. The venocontractions induced by dihydroergotamine at a concentration of 0.03 mumol/l were inhibited by the calcium channel blockers in a concentration-dependent manner. Verapamil was most effective, followed by nifedipine and diltiazem. In dihydroergotamine-precontracted veins nifedipine produced a more pronounced relaxation than verapamil. Lanthanum chloride (5 mmol/l) inhibited the dihydroergotamine-induced contraction by about 90%. Exposure of veins to a calcium-free medium for 30 min resulted in an inhibition of the dihydroergotamine-induced venocontraction by more than 90%. The addition of calcium ions to the medium caused an increase in the contraction with a maximum which closely resembled that of the control. The present studies demonstrate that the contractile response of human femoral veins to dihydroergotamine depends to a great extent on extracellular calcium. However, the calcium channel blockers verapamil, diltiazem and nifedipine, inhibit the agonist-induced venocontractions in part only.