Vasoconstrictor effect and mechanism of action of endothelin-1 in human radial artery and vein: Implication of skin flap vasospasm

Vasospasm in the vascular pedicle is a major cause of ischemic necrosis in autogenous skin transplantation (i.e., skin free flap surgery), and the pathophysiology is unclear. The clinical impression is that veins are more susceptible to vasospasm than arteries in the vascular pedicle of skin free flaps. The purpose of this study was to compare the vasoconstrictor response of the human radial artery (RA) and radial vein (RV) to endothelin (ET)-1 and to investigate the mechanism mediating ET-1-induced vasoconstriction. The isometric tension of RA and RV rings (4 mm) obtained from the vascular pedicle of human radial forearm skin free flaps were studied in organ chambers containing Krebs bicarbonate buffer. It was observed that ET-1 elicited concentration-dependent (5 x 10(-11) to 2 x 10(-8) M contractions in RA and RV rings with similar contractile potency. However, the concentration-dependent contractile response to ET-1 was significantly (P < 0.05) higher in RV rings than in RA rings, with the maximum contractile response twice as high in RV rings than in RA rings. The contractile response to ET-1 in RA and RV rings was blocked by the ETA receptor antagonist BQ 123 (10(-5) M), but not by the ETB receptor antagonist BQ 788 (5 x 10(-6) M). The ETB receptor agonist BQ 3020 (10(-10) to 2 x 10(-8) M had no significant contractile effect in RA and RV rings. Furthermore, the L-type Ca2+ channel antagonist nifedipine (5 x 10(-6) M), the protein kinase C (PKC) inhibitor chelerythrine (10(-5) M), and the intracellular Ca2+ chelator BAPTA-AM (10(-5) M) significantly reduced the contractile potency of ET-1 in RA rings and the maximum contractile response to ET-1 in RA and RV rings. It was concluded that the human RV is more responsive than RA to the contractile effect of ET-1. The contractile response to ET-1 in RA and RV is predominantly mediated by ETA receptors and the postreceptor mechanism involves L-type Ca2+ channels, PKC, and intracellular Ca2+.