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(Hypertension. 2009;54:910.)
© 2009 American Heart Association, Inc.

Original Articles

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

Jeremy P. Langrish; Magnus Lundbäck; Nicholas L. Mills; Neil R. Johnston; David J. Webb; Thomas Sandström; Anders Blomberg; David E. Newby

From the Centre for Cardiovascular Sciences (J.P.L., N.L.M., N.R.J., D.J.W., D.E.N.), University of Edinburgh, Edinburgh, United Kingdom; Department of Medicine, Division of Respiratory Medicine and Allergy, Umeå University Hospital (M.L., T.S., A.B.), Umeå, Sweden.

Correspondence Jeremy P. Langrish, Centre for Cardiovascular Sciences, University of Edinburgh, Room SU.305, Chancellor’s Building, 49 Little France Crescent, Edinburgh EH16 4SB, United Kingdom. E-mail jeremy.langrish{at}ed.ac.uk

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 µg/m³). 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 (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 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.

Key Words: air pollution • particulate matter • endothelial function • endothelin receptor antagonists • ET-1 • endothelin-1 • blood pressure