Effects of ethinyl estradiol, estradiol, and testosterone on hindlimb endothelial function in vivo

Abstract

This study was designed to evaluate the effects of chronic treatment with estrogen and testosterone on hindlimb vascular function. Spontaneously hypertensive rats (SHR) were sham-operated (SHAM) or ovariectomized and treated with vehicle (OVX), ethinyl estradiol (OVX-EE2), estradiol (OVX-E2), or testosterone (OVX-TESTO) for 3 weeks. Anesthetized SHR were instrumented for the measurement of arterial blood pressure and hindlimb blood flow. Ovariectomy had no significant effect on hindlimb resistance. Resting blood pressure (mm Hg) and hindlimb resistance (mm Hg/ml/min/kg) were higher in OVX-TESTO (158 +/- 4 and 4.7 +/- 0.3) than SHAM control (130 +/- 6 and 3.3 +/- 0.4), OVX (139 +/- 6 and 3.4 +/- 0.3), OVX-EE2 (130 +/- 4 and 3.0 +/- 0.3), and OVX-E2 (120 +/- 4 and 3.3 +/- 0.4). The hemodynamic responses to the endothelium-dependent vasodilator acetylcholine (ACh) were similar in SHAM, OVX, OVX-EE2, and OVX-E2. The hindlimb vasodilatory effects of ACh were consistently greater in OVX-TESTO compared with OVX, OVX-EE2, OVX-E2, and SHAM control rats. The hemodynamic responses to the nitric oxide donor, sodium nitroprusside, were similar in all groups. Our results provide evidence of modulatory influence of testosterone on vasomotor function. It is suggested that the enhanced hindlimb endothelial function represents a compensatory mechanism for testosterone-induced hypertension.