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Diesel Exhaust-Induced Pulmonary and Cardiovascular Impairment: The Role of Hypertension Intervention
Citation:
Kodavanti, U., R. Thomas, A. Ledbetter, M. Schladweiler, V. Bass, Todd Krantz, C. King, A. Nyska, J. Richards, D. Andrews, AND Ian Gilmour. Diesel Exhaust-Induced Pulmonary and Cardiovascular Impairment: The Role of Hypertension Intervention. TOXICOLOGICAL AND APPLIED PHARMICOLOGY. Elsevier Science BV, Amsterdam, Netherlands, 268(2):232-40, (2013).
Impact/Purpose:
Underlying cardiovascular diseases have been associated with exacerbated PM effects and systolic BP. However, the role of preexistent hypertension in modifying systemic and pulmonary response to air pollution is not clearly understood. we show that pulmonary protein leakage and atherogenic vascular effects of long-term DE exposures can be effectively reversed by normalizing BP in hypertensive rats. However, the effects of DE on aortic vasoactivity markers are more similar to the effect of BP lowering hydralazine, emphasizing the contribution of peripheral vasculature in regulation of hypertension.
Description:
Background–Exposure to diesel exhaust (DE) particles and associated gases is linked to cardiovascular impairments; however the susceptibility of hypertensive individuals is less well understood. Objective–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. Methods and Results–Male Wistar Kyoto (WKY) rats were treated with hydralazine to reduce blood pressure (BP) or I-NAME to increase BP. Spontaneously hypertensive (SH) rats were treated with hydralazine to decrease BP. Control and drug-pretreated rats were exposed to air, particle-filtered exhaust (gas) or whole-DE (1500 ug/m3), 5hr/d for 2-day or 5d/week for 4-week. Hydralazine decreased BP in SH while L-NAME increased BP in WKY. Acute gas and DE exposures increased neutrophils in lavage fluid; neither drug changed this response. Gas or DE (2-day and 4-week) caused pulmonary protein leakage. This was reversed by hydralazine in SH and increased by L-NAME in WKY. Two-day DE increased serum fatty acid binding protein-3 (FABP-3) in WKY. Hydralazine (not L-NAME) tended to increase FABP-3 in WKY. Marked increases occurred in aortic mRNA after 4-week DE in SH (eNOS, TF, tPA, TNF-, MMP-2, RAGE, and HMGB-1). Hydralazine pre-treatment reversed TF, tPA, TNF-, and MMP-2 expression but not eNOS, RAGE and HMGB-1. eNOS was increased by hydralazine in SH and decreased by L-NAME in WKY. ET-1 was decreased by HYD consistent with its BP lowering effect. Conclusions–Antihypertensive drug treatment reduces gas and DE-induced pulmonary protein leakage and expression of vascular atherogenic markers.