title: Diesel exhaust induced pulmonary and cardiovascular impairment: the role of hypertension intervention.
abstract: Exposure to diesel exhaust (DE) and associated gases is linked to cardiovascular impairments; however, the susceptibility of hypertensive individuals is poorly understood. The objectives of this study were (1) to determine cardiopulmonary effects of gas-phase versus whole-DE and (2) to examine the contribution of systemic hypertension in pulmonary and cardiovascular effects. Male Wistar Kyoto (WKY) rats were treated with hydralazine to reduce blood pressure (BP) or l-NAME to increase BP. Spontaneously hypertensive (SH) rats were treated with hydralazine to reduce BP. Control and drug-pretreated rats were exposed to air, particle-filtered exhaust (gas), or whole DE (1500μg/m(3)), 4h/day for 2days or 5days/week for 4weeks. Acute and 4-week gas and DE exposures increased neutrophils and γ-glutamyl transferase (γ-GT) activity in lavage fluid of WKY and SH rats. DE (4weeks) caused pulmonary albumin leakage and inflammation in SH rats. Two-day DE increased serum fatty acid binding protein-3 (FABP-3) in WKY. Marked increases occurred in aortic mRNA after 4-week DE in SH (eNOS, TF, tPA, TNF-α, MMP-2, RAGE, and HMGB-1). Hydralazine decreased BP in SH while l-NAME tended to increase BP in WKY; however, neither changed inflammation nor BALF γ-GT. DE-induced and baseline BALF albumin leakage was reduced by hydralazine in SH rats and increased by l-NAME in WKY rats. Hydralazine pretreatment reversed DE-induced TF, tPA, TNF-α, and MMP-2 expression but not eNOS, RAGE, and HMGB-1. ET-1 was decreased by HYD. In conclusion, antihypertensive drug treatment reduces gas and DE-induced pulmonary protein leakage and expression of vascular atherogenic markers.
authors: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development (ORD), U.S. Environmental Protection Agency (EPA), Research Triangle Park, NC 27711, USA. kodavanti.urmila@epa.gov
authors: Urmila P
authors: UP
authors: Kodavanti
authors: Ronald F
authors: RF
authors: Thomas
authors: Allen D
authors: AD
authors: Ledbetter
authors: Mette C
authors: MC
authors: Schladweiler
authors: Virginia
authors: V
authors: Bass
authors: Q Todd
authors: QT
authors: Krantz
authors: Charly
authors: C
authors: King
authors: Abraham
authors: A
authors: Nyska
authors: Judy E
authors: JE
authors: Richards
authors: Debora
authors: D
authors: Andrews
authors: M Ian
authors: MI
authors: Gilmour
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000503:physiopathology; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D008171:Lung Diseases / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010974:Platelet Aggregation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000418:Albumins; D001335:Vehicle Emissions; D006830:Hydralazine; D019331:NG-Nitroarginine Methyl Ester