BackgroundLow endogenous testosterone levels have been shown to be a risk factor for the development of cardiovascular disease and cardiovascular benefits associated with testosterone replacement therapy are being advocated; however, the effects of endogenous testosterone levels on acute coronary vasomotor responses to androgen administration are not clear. The objective of this study was to compare the effects of acute androgen administration on in vivo coronary conductance and in vitro coronary microvascular diameter in intact and castrated male swine.MethodsPigs received intracoronary infusions of physiologic levels (1–100 nM) of testosterone, the metabolite 5α-dihydrotestosterone, and the epimer epitestosterone while left anterior descending coronary blood flow and mean arterial pressure were continuously monitored. Following sacrifice, coronary arterioles were isolated, cannulated, and exposed to physiologic concentrations (1–100 nM) of testosterone, 5α-dihydrotestosterone, and epitestosterone. To evaluate effects of the androgen receptor on acute androgen dilation responses, real-time PCR and immunohistochemistry for androgen receptor were performed on conduit and resistance coronary vessels.ResultsIn vivo, testosterone and 5α-dihydrotestosterone produced greater increases in coronary conductance in the intact compared to the castrated males. In vitro, percent maximal dilation of microvessels was similar between intact and castrated males for testosterone and 5α-dihydrotestosterone. In both studies epitestosterone produced significant increases in conductance and microvessel diameter from baseline in the intact males. Androgen receptor mRNA expression and immunohistochemical staining were similar in intact and castrated males.ConclusionsAcute coronary vascular responses to exogenous androgen administration are increased by endogenous testosterone, an effect unrelated to changes in androgen receptor expression.

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Low endogenous testosterone levels have previously been shown to be a risk factor for the development of coronary artery disease; however, the effects of endogenous testosterone levels on the acute coronary vasomotor responses to androgen administration are not clear. The objective of this study was to compare the effects of acute androgen administration on in vivo coronary blood flow and in vitro coronary microvascular diameter in intact and castrated adult male swine. Pigs were anesthetized and received intracoronary infusions of physiologic levels (1–100 nM) of testosterone (T), the epimer epitestosterone (EpiT), and the metabolite 5 alpha‐dihydrotestosterone (DHT) while left anterior descending coronary blood flow and mean arterial pressure were continuously monitored. Following sacrifice, coronary arterioles were isolated, cannulated, and exposed to physiologic concentrations (1–100 nM) of T, EpiT, and DHT. In vivo, T, EpiT, and DHT produced greater increases in coronary conductance in the intact compared to the castrated males. Similarly, in vitro, percent maximal dilation of microvessels was greater in the intact compared to the castrated males for T, EpiT, and DHT. In conclusion, increases in coronary blood flow and coronary arteriolar relaxation in response to acute androgen administration are influenced by endogenous androgen status. Supported by NIH HL071574.