Age, Gender, and Hormonal Status Modulate the Vascular Toxicity of the Diesel Exhaust Extract Phenanthraquinone

Abstract

Inhaled airborne pollutants such as particulate matter increase the susceptibility to adverse health consequences and cardiovascular events. Diesel exhaust contributes significantly to the ambient particle pollution burden. The purpose of this investigation was to determine if exposure to a common component of diesel exhaust, phenanthraquinone (PQ), impairs endothelium-dependent vasodilation of the femoral principal nutrient artery and to determine whether age, gender, and/or hormonal status alter the putative effects of PQ on vasodilation. Vasodilation to acetylcholine (ACh) was assessed in vitro in intact control (age 6, 14, and 24 mo) and ovariectomized (age 6, 14, and 24 mo) female rats and intact (age 6 and 24 mo) male rats. Gender did not influence vasodilator capacity of the femoral principal nutrient artery, and there was an age-related decline in endothelium-dependent vasodilation in both female and male 24-mo-old rats. Exposure to PQ elicited a gender-specific affect in 6-mo-old rats; i.e., vasodilation was impaired 63% in male rats but had no effect in female rats. Exposure to PQ abolished vasodilation in 14- and 24-mo-old rats of both genders, and ovariectomy compromised vasodilator responsiveness to ACh in all age groups. The data demonstrate a vasoprotective mechanism in young female rats that may be related to endogenous ovarian hormones and provides evidence that suggests certain subsets of the population (e.g., elderly, males, and postmenopausal women) may be more susceptible to the adverse consequences of airborne pollutants.

This work was supported by NIH grant HL077224-01 (JMD), a National Heart, Lung, and Blood Institute Postdoctoral Supplement (RDP), and Health Effects Institute grant 4730 (TRN).

Research described in this article was conducted under contract to the Health Effects Institute (HEI), an organization jointly funded by the U.S. Environmental Protection Agency (EPA) (assistance award R-82811201) and certain motor vehicle and engine manufacturers. The contents of this article do not necessarily reflect the views of HEI or its sponsors, nor do they necessarily reflect the views and policies of the U.S. EPA or motor vehicle and engine manufacturers.