Endothelium-independent relaxation of vascular smooth muscle by 17β- estradiol

R. J. Gonzales, N. L. Kanagy

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Background: Estrogens directly dilate arteries, and this acute relaxation of vascular smooth muscle (VSM) may contribute to the cardioprotective effect of this important hormone. However, the mechanism by which estrogens relax VSM is not clear. Methods and Results: Based on observations in isolated smooth muscle cells, we hypothesized that 17β- estradiol (E2) causes dilation through receptor-mediated activation of K+ channels in VSM cells. To test this hypothesis, E2-relaxation was studied in arteries from male Sprague-Dawley rats. We observed that the estrogen receptor antagonist, tamoxifen (3 μmol) attenuated E2 relaxation, suggesting that at least a portion of the relaxation depends on activation of E2 receptors. The nitric oxide synthase inhibitor, Nω-nitro-L-arginine (100 μmol) did not affect E2 relaxation in either denuded or endothelium-intact arterial strips. Furthermore, inhibition of guanylyl cyclase with LY83583 (10 μmol) had no effect on the relaxation, suggesting that nitric oxide does not contribute to this relaxation. Vascular segments contracted with 90 mmol KCl to disrupt the K+ gradient had a similar E2 relaxation to segments contracted with phenylephrine (10-6 mol/L) indicating that E2 relaxation does not require K+-channel activation. Finally, E2 pretreatment inhibited contraction of arterial segments depleted of intracellular calcium but in the presence of extracellular calcium. However, E2 did not affect contraction of strips in calcium-free solution. Conclusions: These final experiments suggest that E2 inhibits Ca2+ influx but not intracellular calcium release. Together, these studies establish that E2 causes receptor-mediated relaxation of peripheral resistance arteries through inhibition of calcium entry independent of nitric oxide production, guanylyl cyclase stimulation, and K+-channel activation.

Original languageEnglish (US)
Pages (from-to)227-234
Number of pages8
JournalJournal of Cardiovascular Pharmacology and Therapeutics
Volume4
Issue number4
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

Keywords

  • Estrogen replacement
  • Estrogens
  • LNNA
  • LY83583
  • Nitric oxide
  • Tamoxifen

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

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