Reversal of endothelin-1-induced vasoconstriction by nifedipine in human resistance vessels in vivo 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 micrograms/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 less than 0.01) in the first minute of infusion and subsequent decreases (to 1.0 +/- .5 ml/min/100 ml, p less than 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 less than 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.
Kiowski
W
W
Department of Medicine, University Hospital, Kantonsspital Basel, Switzerland.
Linder
L
L
D000328:Adult; D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000037:antagonists & inhibitors* / Q000502:physiology; D005260:Female; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D012016:Reference Values; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; D009543:Nifedipine