Affects of Age, Gender, and Estrogen on Endothelium‐Dependent Vasodilation Subsequent to Phenanthraquinone Exposure

Phenanthraquinone (PQ), a compound affixed to diesel exhaust particles, compromises vascular function. In certain populations, particle exposure may exacerbate the impairment. The principal nutrient artery (PNA) is the primary resistance artery that regulates blood flow (BF) to the cortex and marrow in long bones of adult humans and rats. Endothelium‐dependent vasodilation of the PNA declines with aging and corresponds with reduced femoral bone BF. Therefore, exposure of the PNA to PQ could further attenuate skeletal perfusion. The purpose of this study was to 1) Determine whether PQ impairs vasodilation in the PNA and 2) determine whether age, gender, or estrogen alters the presumed effects of PQ. Femoral PNAs from intact and ovariectomized (OVX) female rats (6, 14, and 24 mo) and male rats (6 and 24 mo) were isolated and cannulated. Vasodilation to ACh (10 −9 –10 −4 M) was assessed before and during incubation with PQ (5 μM). Vasodilation was diminished in 24 mo female and male rats. At 6 mo, PQ attenuated vasodilation by ~65% in male rats, but had no effect in female rats. At 14 mo (female rats) and 24 mo (female and male), PQ attenuated and abolished vasodilation, respectively. In all OVX rats, PQ abolished vasodilation. Aging impairs endothelium‐dependent vasodilation. Following the loss of estrogen, particularly at 6 mo where a cardioprotective effect was observed, PQ obliterated vasodilation. Therefore, the ability of the PNA to regulate bone marrow BF could be compromised after diesel particle exposure in males, the elderly, and post‐menopausal women. Supported by the NIH #1 R01 HL077224 ‐01 (JMD).