Abstract
Thromboxane (TXA2), a potent mediator of vasoconstriction, is implicated in the pathogenesis of coronary heart disease (CHD). Recent evidence indicates TXA2-dependent vasoconstriction increases with aging; however, the effects of aging on coronary microvascular reactivity to TXA2 and TXA2 receptor (TP) expression are currently unknown. Females demonstrate reduced vasoconstrictor response to TXA2 and are at lower risk for CHD compared to males until menopause. Therefore, the purpose of this study was to determine the effects of aging and sex on coronary vasoconstrictor response to TXA2, and to determine if aging or sex alters TP protein expression in coronary arterioles. Vascular reactivity to TXA2 analog U46619 was measured in coronary resistance arterioles from young (4 mo) and old (24 mo) male and female (YM, OM, YF, OF) Fisher 344 rats. Aging dramatically reduced U46619-induced vasoconstriction in coronary arterioles from OM compared to those from YM (8 ± 2% vs 53 ± 5%), but had no effect in coronary aterioles from females (OF = 32 ± 11% vs YF = 32 ± 6%). Immunoblot analysis of arteriolar lysates revealed a small increase in TP expression in OM compared to YM, but a dramatic decrease in OF compared to YF. These data indicate both age and gender influence TXA2-induced vasoconstriction in the coronary vasculature. Supported by NIH R01HL077224
Published Version
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