REVERSAL OF ENDOTHELIN-1-INDUCED VASOCONSTRICTION BY NIFEDIPINE IN HUMAN RESISTANCE VESSELS INVIVO IN HEALTHY-SUBJECTS

The influence of blockade of voltage-operated calcium channels by nifedipine on endothelin-1-induced vasoconstriction was investigated in 10 healthy volunteers. Brachial artery infusions of nifedipine (0.25, 0.5, 1 and 3-mu-g/min/100 ml forearm tissue) resulted in dose-dependent increases (mean +/- SD) in forearm blood flow (103 +/- 63% to 833 +/- 426%). Intraarterial infusions of endothelin-1 (50 ng/min/100 ml) resulted in transient increases in forearm blood flow (2.6 +/- 0.9 vs 3.9 +/-2.0 ml/min/100 ml, p < 0.01) in the first minute of infusion and subsequent decreases (to 1.0 +/- .5 ml/min/100 ml, p < 0.01) in the third minute of infusion. Endothelin-1-induced vasoconstriction was reversed by the lowest dose of nifedipine, whereas the higher dosages of nifedipine further increased forearm blood flow to 12.5 +/- 6.4 ml/min/100 ml. The percent increase of forearm blood flow during co-infusion of endothelin-1 and the highest dosage of nifedipine was significantly greater compared with nifedipine alone (1,204 +/- 531 % vs 833 +/-426%, p < 0.05). The results demonstrate a dual action of luminally applied endothelin-1 in human resistance vessels in vivo (e.g., transient initial vasodilation followed by pronounced vasoconstriction) and suggest that blockade of voltage-operated calcium channels can effectively counteract the vasoconstrictor effects of endothelin-1.