Effect of 17beta-estradiol on the Contraction to Endothelin-1 in Porcine Coronary Artery

Jeong, Ho Gyeong; Kang, Byeong Sun; Kim, Min Gu; Park, Byeong Gun; Hwang, Jin Yong; Seo, Bong Gwan

Abstract

OBJECTIVES
It is widely accepted that estrogen has favorable effects on cardiovascular diseases, especially in the postmenopausal women. Endothelin-1(ET-I), released from the vascular endothelium, is a 21-amino acid peptide with strong vasoconstrictor activity. However, the effect of estrogen on the vasoconstriction to ET-1 has not been extensively studied.
METHODS
To investigate the effect of estrogen (175beta-estradiol) on the vascular contraction to ET-1, porcine coronary artery(PCA) rings were suspended in organ chambers(37 degrees C, 95% O2/5% CO2) for measurement of isometric tension change. Endothelium was removed mechanically if necessary. In acute experiments, vascular rings were preincubated for 15minutes with 3different concentrations of 170beta-estradiol(10(-6), 10(-5), 10(-4)M) and concentration-contraction curves to cumulative doses of ET-1 were constructed. In the experiments after a longer exposure to 17beta-estradiol, the vessels with endothelium were exposed in the 5% CO2 incubator to 3different concentrations of 17beta-estradiol(10(-9), 10(-8), 10(-7)M) for 44-50 hours, and then concentrationcontraction curves to ET-1 were obtained.
RESULTS
Incubation for 15minutes with 170beta-estradiol(10(-4)M) inhibited ET-1-induced contraction in the vessels with endothelium(area under the curve and maximal contraction, p<0.05 compared with control). This effect persisted regardless of the sex and the presence or absence of the endotheliurn. Incubation of the vessels far a longer time with 170beta-estradiol(44-50 hours) resulted in the inhibition of maximal contraction to ET-1(p<0.05) by a lower concentration of 175beta-estradiol(10(-7)M) than in acute experiments in male PCA rings, but an enhanced contraction to ET-1(area under the curve; p<0.05) by 10M of 175beta-estradiol was observed in female PCA rings.
CONCLUSION
Short-time incubation with 17Pbeta-estradiol has an inhibitory effect on the contraction to ET-1 in PCA rings. This effect is independent of the presence of the endothelium and the sex of the pigs. A longer incubation with 17beta-estradiol results in a similar inhibitory effect on male(but not female) PCA rings, suggesting that a sex-related difference may exist concerning the effect of 17beta-estradiol on ET-1-induced contraction.