Altered Nitric Oxide Bioavailability Contributes to Diesel Exhaust Inhalation‐Induced Cardiovascular Dysfunction in Man. Issue 1 (19th February 2013)

• Record Type: Journal Article
• Authors: Langrish, Jeremy P.; Unosson, Jon; Bosson, Jenny; Barath, Stefan; Muala, Ala; Blackwell, Scott; Söderberg, Stefan; Pourazar, Jamshid; Megson, Ian L.; Treweeke, Andrew; Sandström, Thomas; Newby, David E.; Blomberg, Anders; Mills, Nicholas L.
• Is Part Of: Journal of the American Heart Association. Volume 2:Issue 1(2013:Feb.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2013-02-19
• Subjects: air pollution -- endothelial function -- nitric oxide -- nitric oxide synthase -- vascular biology; Heart -- Diseases -- Periodicals; Cardiovascular system -- Diseases -- Periodicals; Cerebrovascular disease -- Periodicals; Cardiology -- Periodicals; 616.1
• DOI: 10.1161/JAHA.112.004309
• Languages: English
• ISSNs: 2047-9980

Abstract

Abstract : Background: Diesel exhaust inhalation causes cardiovascular dysfunction including impaired vascular reactivity, increased blood pressure, and arterial stiffness. We investigated the role of nitric oxide (NO) bioavailability in mediating these effects. Methods and Results: In 2 randomized double‐blind crossover studies, healthy nonsmokers were exposed to diesel exhaust or filtered air. Study 1 : Bilateral forearm blood flow was measured during intrabrachial infusions of acetylcholine (ACh; 5 to 20 μg/min) and sodium nitroprusside (SNP; 2 to 8 μg/min) in the presence of the NO clamp (NO synthase inhibitor N G ‐monomethyl‐l ‐arginine (l ‐NMMA) 8 μg/min coinfused with the NO donor SNP at 90 to 540 ng/min to restore basal blood flow). Study 2 : Blood pressure, arterial stiffness, and cardiac output were measured during systemic NO synthase inhibition with intravenousl ‐NMMA (3 mg/kg). Following diesel exhaust inhalation, plasma nitrite concentrations were increased (68±48 versus 41±32 nmol/L; P =0.006) despite similarl ‐NMMA–induced reductions in basal blood flow (−20.6±14.7% versus −21.1±14.6%; P =0.559) compared to air. In the presence of the NO clamp, ACh and SNP caused dose‐dependent vasodilatation that was not affected by diesel exhaust inhalation ( P >0.05 for both). Following exposure to diesel exhaust, l ‐NMMA caused a greater increase in blood pressure ( P =0.048) and central arterial stiffness ( P =0.007), but reductions in cardiac output and increases in systemic vascular resistance ( P >0.05 for both) were similar to those seen with filtered air. Conclusions: Diesel exhaust inhalation disturbs normal vascular homeostasis with enhanced NO generation unable to compensate for excess consumption. We suggest the adverse cardiovascular effects of air pollution are, in part, mediated through reduced NO bioavailability. Clinical Trial Registration: URL:http://www.ClinicalTrials.gov . Unique identifiers: NCT00845767 and NCT01060930.