Nongenomic responses to 17beta-estradiol in male rat mesenteric arteries abolish intrinsic gender differences in vascular responses

Abstract

The aim of the present study was to investigate the gender differences in the acute effects of 17beta-estradiol on the rat superior mesenteric artery. Isometric tension was measured in rings of mesenteric arteries from both male and female Sprague-Dawley rats. Relaxation to acetylcholine was not significantly different between arteries (with endothelium) from male and female rats in the absence or presence of 17beta-estradiol. After blockade of endothelium-dependent hyperpolarizations with apamin (0.3 microM) plus charybdotoxin (0.1 microM), acute exposure to 17beta-estradiol (1 nM) for 30 min resulted in enhancement of relaxation to acetylcholine in arteries from male but not female rats. After acute exposure to 17beta-estradiol, mesenteric arteries from male rats were more sensitive to sodium nitroprusside than arteries from female rats. Contractions of mesenteric arteries to phenylephrine and 9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin F(2alpha) (U46619) were greater in arteries from male rats than female rats. This difference was not detected after acute exposure to 17beta-estradiol. In preparations without endothelium, the enhancement of relaxation and reduction in contraction in arteries from male rats were preserved. These results suggest that there exists a gender difference in the response to the acute nongenomic modulatory effect of 17beta-estradiol in rat mesenteric arteries. Arteries from male rats seem to be more sensitive to the modulatory effects of 17beta-estradiol than arteries from female rats. The effect appears to be mainly at the level of the vascular smooth muscles.

Figure 1

Effects of 17β-estradiol on acetylcholine-induced relaxation. Rings from superior mesenteric arteries of male and female rats were incubated with either vehicle control or 17β-estradiol (1 nM) for 30 min. Rings were then contracted with phenylephrine (1 μM) before acetylcholine was added cumulatively. Data are expressed as mean±s.e.m. with n=5–7. (a) Concentration–response curves to acetylcholine after exposure to 17β-estradiol. (b) Relaxation expressed as area under concentration–response curves.

Figure 2

Effects of 17β-estradiol on EDHF component of acetylcholine-induced relaxation. Rings from superior mesenteric arteries of male and female rats were incubated with L-NAME (300 μM) together with either vehicle control or 17β-estradiol (1 nM) for 30 min. Rings were then contracted with phenylephrine (1 μM) before acetylcholine was added cumulatively. Data are expressed as mean±s.e.m. with n=6–7. (a) Concentration–response curves to acetylcholine after exposure to 17β-estradiol. (b) Relaxation expressed as area under concentration–response curves.

Figure 3

Effects of 17β-estradiol on NO component of acetylcholine-induced relaxation. Rings from superior mesenteric arteries of male and female rats were incubated with apamin (300 nM) and charybdotoxin (100 nM) together with either vehicle control or 17β-estradiol (1 nM) for 30 min. Rings were then contracted with phenylephrine (1 μM) before acetylcholine was added cumulatively. Data are expressed as mean±s.e.m. with n=6–7. (a) Concentration–response curves to acetylcholine after exposure to 17β-estradiol. ^*P<0.05 vs all groups. (b) Relaxation expressed as area under concentration–response curves. ^*P<0.05 vs male control group (ANOVA followed by post hoc Dunnett's test).

Figure 4

Effects of 17β-estradiol on sodium nitroprusside-induced relaxation. Rings from superior mesenteric arteries of male and female rats were incubated with either vehicle control or 17β-estradiol (1 nM) for 30 min. Rings were then contracted with phenylephrine (1 μM) before sodium nitroprusside was added cumulatively. Data are expressed as mean±s.e.m. with n=6–7. (a) Concentration–response curves to sodium nitroprusside after exposure to 17β-estradiol. ^*P<0.05 vs all groups. (b) Relaxation expressed as area under concentration–response curves. ^*P<0.05 vs male control group (ANOVA followed by post hoc Dunnett's test).

Figure 5

Effects of 17β-estradiol on phenylephrine-induced contraction. Rings from superior mesenteric arteries of male and female rats were incubated with either vehicle control or 17β-estradiol (1 nM) for 30 min. Phenylephrine was then added cumulatively. Responses were expressed as tension in grams. Data are expressed as mean±s.e.m. with n=6–7. (a) Concentration–response curves to phenylephrine after exposure to 17β-estradiol. ^*P<0.05 vs all groups. (b) Contraction expressed as area under concentration–response curves. ^*P<0.05 vs male control group (ANOVA followed by post hoc Dunnett's test).

Figure 6

Effects of 17β-estradiol on U46619-induced contraction. Rings from superior mesenteric arteries of male and female rats were incubated with either vehicle control or 17β-estradiol (1 nM) for 30 min. U46619 was then added cumulatively. Responses were expressed as tension in grams. Data are expressed as mean±s.e.m. with n=6–7. (a) Concentration–response curves to U46619 after exposure to 17β-estradiol. ^*P<0.05 vs all groups. (b) Contraction expressed as area under concentration–response curves. ^*P<0.05 vs male control group (ANOVA followed by post hoc Dunnett's test).

Figure 7

Effects of 17β-estradiol on phenylephrine-induced contraction and sodium nitroprusside-induced relaxation. Endothelium disrupted rings from superior mesenteric arteries of male rats were incubated with either vehicle or 17β-estradiol for 30 min. (a) Rings were contracted with phenylephrine (1 μM) before sodium nitroprusside was added cumulatively. (b) Phenylephrine was added cumulatively. Responses were expressed as tension in grams. Data are expressed as mean±s.e.m. with n=6–7. ^*P<0.05 vs male control group (ANOVA followed by post hoc Dunnett's test).