Endothelium-dependent and independent enhancement of vascular contractility in the ovariectomized rabbit.
OBJECTIVE
Estrogen suppresses contractile response and increases vasodilator response, partly by modulating endothelial function. However, the effect of estrogen on the contractility of vascular smooth muscle remains to be elucidated. We investigated the effect of a long-term estrogen deficiency on vascular contractility and the Ca(2+) sensitivity of the contractile apparatus in arterial smooth muscle.


METHODS
Female rabbits were divided into the following three groups: control group, an ovariectomized group (OVX), and a group supplemented with 17beta-estradiol after ovariectomy (OVX+E2). Twelve weeks later, the mesenteric artery was isolated, and the vascular contractility was evaluated.


RESULTS
In OVX, the contractile responses to phenylephrine and 118 mM potassium were enhanced, and the basal release of nitric oxide decreased in the strips with endothelium compared with either OVX+E2 or control. An enhancement of contraction was also observed in the strips without endothelium. However, the extent of enhancement was smaller than that observed in the presence of endothelium. The simultaneous measurement of calcium ([Ca(2+)](i)) and tension revealed no significant difference in the [Ca(2+)](i) elevations induced by phenylephrine among the three groups. In the alpha-toxin permeabilized strips, the Ca(2+)-tension relationships obtained both with and without phenylephrine and guanosine triphosphate were similar among the three groups. No difference in the myosin expression and the histology of vascular tissue was observed among the three groups.


CONCLUSIONS
Long-term estrogen deficiency increased the vascular tone mainly by enhancing smooth muscle contractility. Endothelial dysfunction is considered to play a minor role in the augmentation of vascular tone.
Koga
Miho
M
Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Hirano
Katsuya
K
Nishimura
Junji
J
Nakano
Hitoo
H
Kanaide
Hideo
H
D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010052:Ovariectomy; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits
D010656:Phenylephrine