Gender differences in the endothelin-B receptor contribution to resting vascular tone in humans

Endothelin-1 can contribute to vascular tone through endothelin-A (ETA) receptors and/or endothelin-B (ETB) receptors of 2 subtypes: ETB1 mediating vasodilation; and ETB2 mediating vasoconstriction. To test whether ETB receptors contribute to vascular tone, we administered an ETB antagonist, BQ-788 by intradermal microdialysis in the forearm skin of 8 subjects: 4 male and 4 female. BQ-788 doses were 150 nM, 600 nM, and 2400 nM. Skin blood flow was indexed by laser-Doppler flowmetry (LDF) at the microdialysis site. Mean arterial pressure (MAP) was measured (Finapres) and cutaneous vascular conductance (CVC) calculated (CVC=LDF/MAP). The microdialysis probes were perfused at 2ml/min with Ringers solution followed by the 3 doses of BQ-788 and finally with 28mM sodium nitroprusside to cause maximal vasodilation. CVC's were normalized and expressed as a percentage of this maximal value. Average CVC's in males were: 18+/-6%max (baseline); 24+/-7%max (150 nM); 27+/-8%max (600 nM); and 31+/-7% (2400 nM). Average CVC's in females were: 10±2%max (baseline); 8+/-2%max (150 nM); 12+/-1%max (600 nM); and 16+/-2% (2400 nM). Overall, CVC increased with increasing doses of BQ-788 (p<0.05) and these increases differed with gender (p<0.05). Non-selective blockade of ETB receptors caused dose-dependent a cutaneous vasodilation that differed with gender. We conclude that ETB receptors, predominantly of the ETB2 subtype, mediate a tonic vasoconstriction in the human cutaneous vasculature and that this vasoconstriction is greater in males than females.