title: Bone medullary arterioles from ovariectomized rats have smaller baseline diameters but normal eNOS expression and NO-mediated dilation.
abstract: This study was designed to test the hypothesis that endogenous estrogens decrease the expression of endothelial nitric oxide synthase (eNOS) in resistance-size bone arterioles, thereby reducing endothelium-dependent vasodilator function. Sexually mature female rats were ovariectomized to reduce endogenous estrogens. Age-matched female rats served as controls. Seven to ten days after ovariectomy, bone marrow tissue was collected from the femoral canal. Immuno-histochemistry was performed to detect expression of estrogen receptors, alpha and beta and eNOS. eNOS protein content in medullary bone arterioles was compared using Western blot analysis. Endothelial cell function was assessed by quantitating the dilation of isolated, pressurized bone arterioles in response to acetylcholine. The results indicate that the endothelium of bone arterioles from ovariectomized and control rats express ER-alpha, ER-beta and eNOS. eNOS protein content in the two groups of arterioles did not differ. However, the baseline diameter of arterioles from ovariectomized rats (63+/-4 microm) was significantly smaller than the diameter of arterioles from control rats (75+/-3 microm, p<0.05). The two groups of arterioles dilated equally in response to acetylcholine. L-NAME, an inhibitor of eNOS, almost completely abolished the dilator responses to acetylcholine, but not to sodium nitroprusside. L-Arginine restored acetylcholine-induced dilation after L-NAME treatment. Thus, arteriole dilation to acetylcholine appears to be mediated almost exclusively by NO. The smaller diameter of arterioles from ovariectomized rats suggests that endogenous estrogens exert a significant dilator influence on bone arterioles. However, the dilator influence does not appear to be mediated by an increase in eNOS expression or enhanced NO-dependent vasodilation. These results indicate that estrogens do not decrease eNOS expression or diminish NO-mediated dilation of bone medullary arterioles.
authors: Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40292, USA.
authors: Galia
authors: G
authors: Soukhova-O'Hare
authors: Zhenmin
authors: Z
authors: Lei
authors: Jeff C
authors: JC
authors: Falcone
authors: Michelle T
authors: MT
authors: Barati
authors: Jeremy B A
authors: JB
authors: Feitelson
authors: Ch V
authors: ChV
authors: Rao
authors: John T
authors: JT
authors: Fleming
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001160:Arterioles / Q000737:chemistry* / Q000187:drug effects / Q000648:ultrastructure; D001842:Bone and Bones / Q000098:blood supply*; D004727:Endothelium / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000032:analysis; D047629:Estrogen Receptor beta / Q000032:analysis; D004967:Estrogens / Q000502:physiology; D005260:Female; D005269:Femur / Q000098:blood supply; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000032:analysis* / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D010052:Ovariectomy; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester