Testosterone-induced Coronary Conductance and Resistance Vessel Relaxation In Vivo: Potential Mechanisms of Action

Although testostone causes relaxation of the coronary vascular bed, its mechanisms of action has not been defined. We examined the effect of intracoronary testosterone (10−6 to 10−5M) on epicardial and resistance coronary arteries in vivo in 10 dogs (5 male, 5 female). Changes in coronary average peak velocity (APV) were assessed using 0.014″ Doppler guidewire (Cardiometrics), and epicardial cross-sectional are (CSA) was measured using 4.3F, 30 MHz ultrasound imaging catheter (CVIS). After establishing baseline response, the contribution of nitric oxide (NO), prostaglandins and ATP-sensitive K+ channels was assessed. Testosterone induced significant increase in both CS and APV at the 10−6 and 10−5M concentrations (CSA: 12.6 ± 5.0 and 13.7 ± 8.8%, APV: 53.5 ± 21.9% and 37.8 ± 12.2% at 10−6 and 10−5M respectively (p < 0.01 in all cases)). Pre-treatment withω Nitro-L-arginine methylester (L-NAME, 100 μM intracoronary) to block NO synthesis decreased testosterone-induced increase in CS (13.4 vs. 8.0%, P = 0.06) and APV (89.4% vs. 39.8%, P = 0.06). Pre-treatment with glibenclamide (10−5M) to assess role of ATP-sensitive K+ channels did not attenuate testosterone-induced dilation in epicardial arteries though it did in the microcirculation (74.8 vs. 32.8%, P = 0.03). Pre-treatment with indomethacin (5 mg/kg IV) did not alter changes. Conclusion: We conclude that acute testosterone-induced conductance coronary vasorelaxation is mediated in part by endothelium-derived NO. In contrast, ATP-sensitive K+ channels appear to modulate testosterone effects on resistance arteries. The prostanoid system is not involved in either conductance or resistance coronary vascular relaxation.