Previous clinical studies have demonstrated that estrogens have a cardioprotective effect. This is supported by the observation that estrogen relaxes vascular smooth muscle (VSM). However, the mechanism by which estrogen relaxes VSM is not clear. Based on published observations in coronary arteries, we hypothesized that 17β-estradiol (E2) relaxes VSM through receptor-mediated activation of NO production in smooth muscle cells. To test this hypothesis. E2-relaxation was studied in helical arterial strips contracted with either phenylephrinc (10-6 M) or KCl (90 mM). Tail and mesenteric arteries from male Sprague-Dawley rats were used to examine the dependence of E2 relaxation on receptor stimulation using the anti-estrogen agent, tamoxifen (3 μM). E2 relaxation in denuded and endothelium intact arterial strips was determined by inhibiting NO synthase using Nω-nitro-L-arginine (100 μM) while the involvement of guanylyl cyclase stimulation was examined using the guanylyl cyclase inhibitor LY83583 (10 mM). Studies confirmed that E2 directly relaxes arterial segments independent of the presence of endothelium. The mechanism of this relaxation was found to be independent of NO production and guanylyl cyclase stimulation. In the presence of 90 mM KCl, relaxation was not impaired indicating that K-channel activation does not play a role in this response. Tamoxifen studies indicated that E2 vasorelaxation is receptor mediated while responses to strips with depleted calcium stores suggest that E2 may inhibit calcium influx.
|Original language||English (US)|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology