ESTROGEN REPLACEMENT ATTENUATES RESISTANCE ARTERY ADRENERGIC SENSITIVITY VIA ENDOTHELIAL VASODILATORS

The objective of this study was to determine whether chronic estrogen replacement alters adrenergic constriction and endothelium-dependent d ilation in resistance arteries from the rat. Resistance-sized (< 200 m u m) mesenteric arteries from castrated female Sprague-Dawley rats wit h (E2; 21 day, 0.5-mg pellet) and without (OvX) estrogen replacement w ere removed for in vitro study on a pressurized arteriograph system. S ensitivity to alpha-adrenergic constriction and the role of the endoth elium in its modulation and of agonist-provoked endothelium-dependent relaxation were determined. Estrogen-treated rats had decreased heart rate as well as systolic and diastolic blood pressure. Arteries from e strogen-replaced rats were fivefold less sensitive to alpha(1)-adrener gic stimulation with phenylephrine (50% effective concentration: E2, 3 .2 +/- 1.1 mu M; OvX, 0.6 +/- 0.2 mu M; P < 0.05). This difference was abolished by endothelial denudation, blockade of cyclooxygenase (1 mu M ibuprofen), or nitric oxide synthase blockade (0.24 mM N-omega-nitr o-L-arginine). There was no difference in muscarinic agonist-provoked relaxation or vascular smooth muscle sensitivity to prostacyclin or so dium nitroprusside. These results indicate that estrogen replacement d ecreases resistance artery adrenergic sensitivity by increasing the ba sal release of relaxing factors from the endothelium. This effect on s mall artery function may produce dual cardioprotective effects by decr easing peripheral resistance, blood pressure, and the likelihood of th rombosis.