Endothelin antagonists and hypertension: a question of dose?

Abstract

To the Editor: We read with interest the recent report in Hypertension from Martin et al1 on the effects of intra-arterial administration of the endothelin ETA/B receptor antagonist, SB 209670, on forearm blood flow in hypertensive subjects and matched controls. Their finding of forearm vasodilation to intra-arterial SB 209670 in healthy controls suggests a role for endothelin-1 (ET-1) in regulation of basal vascular tone and is consistent with our own work2–4 and that of some,4,5 but not all other groups,6,7 with both ETA receptor selective and ETA/B receptor antagonists. Also, contrary to some earlier work,6,7 they find no difference from controls in the in vivo response of the resistance vessels of hypertensive subjects to ET receptor antagonism. Our early intra-arterial studies were undertaken with the ETA selective antagonist, BQ-123, at a dose of 100 nmol/min.2 We have since undertaken pharmacodynamic and kinetic dose-ranging systemic studies with BQ-123 and find that this …