Endothelin receptor subtype(s) in rabbit jugular vein smooth muscle

The goal of our study was to characterize pharmacologically the receptor subtype(s) that mediate endothelin-induced force development in the rabbit jugular vein. Endothelin-1 (ET-1), sarafotoxin S6c, and the linear endothelin peptide Ala11,15-ET-1[8-21] evoked approximately monophasic concentration-dependent increases in force development in the rabbit jugular vein (rank order of potency: sarafotoxin S6c > ET-1 > Ala11,15-ET-1[8-21]). Maximally effective concentrations of the relatively ETB-selective (in comparison to ETA) ligands sarafotoxin S6c and Ala11,15-ET-1[8-21] produced significantly less force than a maximally effective ET-1 concentration (79 and 78% of ET-1 max., respectively; p < 0.001 for both). ET-3 produced a relatively shallow concentration-force relationship. Force evoked by ET-1 was minimally affected by the relatively ETA-selective (in comparison with ETB) receptor antagonists BQ-123 and FR139317. These data indicate that the dominant functional ET receptor in rabbit jugular vein smooth muscle is of a non-ETA subtype.