Impaired acetylcholine-induced release of nitric oxide in the aorta of male aromatase-knockout mice: regulation of nitric oxide production by endogenous sex hormones in males.
The consequences of estrogen deficiency on the cardiovascular system have been widely examined in females. The effects of endogenous estrogen deficiency in males are less clear. The aromatase-knockout (ArKO) mouse lacks a functional Cyp19 gene, which encodes aromatase, and is thus incapable of synthesizing endogenous estrogen. In the present study, we examined the effect of lack of endogenous estrogens on vascular function in aortic rings isolated from male ArKO mice and compared these effects to rings from wild-type (WT) littermates. Full concentration-response curves to norepinephrine, acetylcholine, isoprenaline, and sodium nitroprusside were obtained in the absence and presence of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine in aortic segments set up in isometric myographs. Responses to noradrenaline were not different in aorta from ArKO compared with WT mice. Both Nomega-nitro-L-arginine and endothelium denudation significantly shifted the noradrenaline concentration-response curve to the left; however, this shift was not different in ArKO compared with WT. Responses to the endothelium-dependent vasodilator acetylcholine were significantly blunted in aortic rings from ArKO mice (Emax, 58.2+/-0.9% and 34.0+/-0.5% in wild-type and ArKO, respectively; P<0.05), whereas responses to the endothelium-independent agonist sodium nitroprusside and to the partial endothelium-dependent agonist isoprenaline were not affected. These findings suggest that endogenous estrogen facilitate vasorelaxation in males. This may be via modulating endothelial function rather than vascular smooth muscle cell responsiveness.
Kimura
Masahiko
M
Alfred and Baker Medical Unit, Wynn Domain, Baker Medical Research Institute, Prahran, Victoria, Australia.
Sudhir
Krishnankutty
K
Jones
Margaret
M
Simpson
Evan
E
Jefferis
Ann-Maree
AM
Chin-Dusting
Jaye P F
JP
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005838:Genotype; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D004967:Estrogens; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D001141:Aromatase; D007545:Isoproterenol; D000109:Acetylcholine; D009638:Norepinephrine