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 dilation in resistance arteries from the rat. Resistance-sized (< 200 microns) mesenteric arteries from castrated female Sprague-Dawley rats with (E2; 21 day, 0.5-mg pellet) and without (OvX) estrogen replacement were removed for in vitro study on a pressurized arteriograph system. Sensitivity to alpha-adrenergic constriction and the role of the endothelium 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 estrogen-replaced rats were fivefold less sensitive to alpha 1-adrenergic stimulation with phenylephrine (50% effective concentration: E2, 3.2 +/- 1.1 microM; OvX, 0.6 +/- 0.2 microM; P < 0.05). This difference was abolished by endothelial denudation, blockade of cyclooxygenase (1 microM ibuprofen), or nitric oxide synthase blockade (0.24 mM N omega-nitro-L-arginine). There was no difference in muscarinic agonist-provoked relaxation or vascular smooth muscle sensitivity to prostacyclin or sodium nitroprusside. These results indicate that estrogen replacement decreases resistance artery adrenergic sensitivity by increasing the basal release of relaxing factors from the endothelium. This effect on small artery function may produce dual cardioprotective effects by decreasing peripheral resistance, blood pressure, and the likelihood of thrombosis.
Meyer
M C
MC
Department of Obstetrics and Gynecology, University of Vermont College of Medicine, Burlington 05401, USA.
Cummings
K
K
Osol
G
G
D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology; D011464:Epoprostenol / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007052:Ibuprofen / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010052:Ovariectomy; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects*; D014666:Vasomotor System / Q000187:drug effects
D018340:Receptors, Adrenergic, alpha-1; D009599:Nitroprusside; D010656:Phenylephrine; D019335:Nitroarginine; D009569:Nitric Oxide; D004958:Estradiol; D011464:Epoprostenol; D007052:Ibuprofen