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Dantas AP, Franco Mdo C, Tostes RC, Fortes ZB, Costa SG, Nigro D, Carvalho MH

Relative contribution of estrogen withdrawal and gonadotropins increase secondary to ovariectomy on prostaglandin generation in mesenteric microvessels.

J. Cardiovasc. Pharmacol.. 2004 Jan;43(1):48-55, PMID: 14668567

Recent studies have established that ovariectomy impairs endothelial function, partially by increasing vasoconstrictor prostaglandins generation. Because ovariectomy causes concomitant lack of estrogen and increase of gonadotropins (ie, LH and FSH), in this study we explored the relative role of estrogen and LH/FSH in modulating vasoconstrictor prostaglandins generation in mesenteric arteriolar bed of SHR. Endothelium-dependent relaxation to acetylcholine (ACh) and bradykinin (Bk) was markedly reduced in ovariectomized (OVX) compared with SHR in physiological estrus (OE). Estrogen replacement (OVX + E), but not the decrease in LH/FSH levels with leuprolide (OVX + Leu), corrected the altered vasorelaxation response in OVX. Treatment of mesenteries with diclofenac, prostaglandin-H synthase (PGHS) inhibitor, significantly enhanced the relaxing response in arteries from OVX and OVX + Leu, but not those from OE, indicating that a PGHS-derived vasoconstrictor has modified the endothelium-dependent response during estrogen but not LH/FSH deprivation. Confirming these data, in response to exogenous arachidonic acid, whereas arteries from OVX and OVX + Leu exhibited a marked and similar vasoconstrictor response, the arteries from OE and OVX + E rats exhibited a slight vasodilation. We also demonstrated by RT-PCR that ovariectomy significantly increased PGHS-2 but not PGHS-1 mRNA expression in comparison to OE. The PGHS-2 overexpression in OVX was corrected by estrogen replacement, but not by the reduction of LH/FSH levels. Altogether these data strongly support a role for hypoestrogenism rather than LH/FSH enhancement, associated with the removal of ovaries, in the increase of vasoconstrictor prostaglandins, possibly by a mechanism involving PGHS-2 overexpression.


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