Contribution of endothelin-1 to the vascular effects of diesel exhaust inhalation in humans
2009 (English)In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 54, no 4, 910-915 p.Article in journal (Refereed) Published
Diesel exhaust inhalation impairs vascular function, and, althoughthe underlying mechanism remains unclear, endothelin (ET) 1and NO are potential mediators. The aim of this study was toidentify whether diesel exhaust inhalation affects the vascularactions of ET-1 in humans. In a randomized, double-blind crossoverstudy, 13 healthy male volunteers were exposed to either filteredair or dilute diesel exhaust (331±13 µg/m3). Plasmaconcentrations of ET-1 and big-ET-1 were determined at baselineand throughout the 24-hour study period. Bilateral forearm bloodflow was measured 2 hours after the exposure during infusionof either ET-1 (5 pmol/min) or the ETA receptor antagonist,BQ-123 (10 nmol/min) alone and in combination with the ETB receptorantagonist, BQ-788 (1 nmol/min). Diesel exhaust exposure hadno effect on plasma ET-1 and big-ET-1 concentrations (P>0.05for both) or 24-hour mean blood pressure or heart rate (P>0.05for all). ET-1 infusion increased plasma ET-1 concentrationsby 58% (P<0.01) but caused vasoconstriction only after dieselexhaust exposure (–17% versus 2% after air; P<0.001).In contrast, diesel exhaust exposure reduced vasodilatationto isolated BQ-123 infusion (20% versus 59% after air; P<0.001)but had no effect on vasodilatation to combined BQ-123 and BQ-788administration (P>0.05). Diesel exhaust inhalation increasesvascular sensitivity to ET-1 and reduces vasodilatation to ETAreceptor antagonism despite unchanged plasma ET-1 concentrations.Given the tonic interaction between the ET and NO systems, weconclude that diesel exhaust inhalation alters vascular reactivityto ET-1 probably through its effects on NO bioavailability.
Place, publisher, year, edition, pages
Dallas, Tex.: The Association , 2009. Vol. 54, no 4, 910-915 p.
air pollution, particulate matter, endothelial function, endothelin receptor antagonists, ET-1, endothelin-1, blood pressure
Respiratory Medicine and Allergy
IdentifiersURN: urn:nbn:se:umu:diva-27792DOI: 10.1161/HYPERTENSIONAHA.109.135947OAI: oai:DiVA.org:umu-27792DiVA: diva2:277746