Contribution of Endothelin 1 to the Vascular Effects of Diesel Exhaust Inhalation in Humans

Diesel exhaust inhalation impairs vascular function, and, although the underlying mechanism remains unclear, endothelin (ET) 1 and NO are potential mediators. The aim of this study was to identify whether diesel exhaust inhalation affects the vascular actions of ET-1 in humans. In a randomized, double-blind crossover study, 13 healthy male volunteers were exposed to either filtered air or dilute diesel exhaust (331 +/- 13 mu g/m(3)). Plasma concentrations of ET-1 and big-ET-1 were determined at baseline and throughout the 24-hour study period. Bilateral forearm blood flow was measured 2 hours after the exposure during infusion of either ET-1 (5 pmol/min) or the ETA receptor antagonist, BQ-123 (10 nmol/min) alone and in combination with the ETB receptor antagonist, BQ-788 (1 nmol/min). Diesel exhaust exposure had no effect on plasma ET-1 and big-ET-1 concentrations (P > 0.05 for both) or 24-hour mean blood pressure or heart rate (P > 0.05 for all). ET-1 infusion increased plasma ET-1 concentrations by 58% (P < 0.01) but caused vasoconstriction only after diesel exhaust exposure (-17% versus 2% after air; P < 0.001). In contrast, diesel exhaust exposure reduced vasodilatation to isolated BQ-123 infusion (20% versus 59% after air; P < 0.001) but had no effect on vasodilatation to combined BQ-123 and BQ-788 administration (P > 0.05). Diesel exhaust inhalation increases vascular sensitivity to ET-1 and reduces vasodilatation to ETA receptor antagonism despite unchanged plasma ET-1 concentrations. Given the tonic interaction between the ET and NO systems, we conclude that diesel exhaust inhalation alters vascular reactivity to ET-1 probably through its effects on NO bioavailability. (Hypertension. 2009; 54: 910-915.)