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

Abstract

Abstract-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 (331Ϯ13 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 ET A receptor antagonist, BQ-123 (10 nmol/min) alone and in combination with the ET B receptor antagonist, BQ-788 (1 nmol/min). Diesel exhaust exposure had no effect on plasma ET-1 and big-ET-1 concentrations (PϾ0.05 for both) or 24-hour mean blood pressure or heart rate (PϾ0.05 for all). ET-1 infusion increased plasma ET-1 concentrations by 58% (PϽ0.01) but caused vasoconstriction only after diesel exhaust exposure (Ϫ17% versus 2% after air; PϽ0.001). In contrast, diesel exhaust exposure reduced vasodilatation to isolated BQ-123 infusion (20% versus 59% after air; PϽ0.001) but had no effect on vasodilatation to combined BQ-123 and BQ-788 administration (PϾ0.05). Diesel exhaust inhalation increases vascular sensitivity to ET-1 and reduces vasodilatation to ET A 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.

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Effects of Chalk Use on Dust Exposure and Classroom Air Quality

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Particulate Matter in New Technology Diesel Exhaust (NTDE) is Quantitatively and Qualitatively Very Different from that Found in Traditional Diesel Exhaust (TDE)

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