Vasorelaxant effects of oestradiols on guinea pigs: a role for gender differences

Naderali, Ebrahim K.; Smith, S. Jerrod; Doyle, P.; Williams, Gareth

doi:10.1046/j.1365-2362.2001.00801.x

“…Furthermore, despite a larger increase in total body weight of obese male rats, attenuation of AChinduced vasodilatation was more pronounced in obese female rats than in obese male rats, indicating a genderdependent variation in vascular reactivity. Similar observations have also been reported previously implying an effect of gender on vascular contractility [25][26][27].…”

Section: Discussionsupporting

confidence: 91%

Dietary obesity in the rat induces endothelial dysfunction without causing insulin resistance: a possible role for triacylglycerols

Naderali¹,

BROWN²,

PICKAVANCE³

et al. 2001

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Impaired arterial vasorelaxation, due primarily to endothelial dysfunction, is associated with obesity. To clarify the relationship with insulin resistance and other metabolic disturbances, we studied endothelial-dependent and -independent vascular responses in rats with dietary-induced obesity. Dietary-obese rats had significantly higher body weights (10-32%; P<0.001) and fat-pad masses (220-280%; P<0.001) than lean controls, together with raised plasma levels of triacylglycerols (15-80%; P<0.001), non-esterified fatty acids (13-38%; P<0.05) and leptin (85-180%; P<0.001). However, measures of insulin sensitivity (including the hyperinsulinaemic-euglycaemic clamp in a parallel experiment) were comparable with those in controls. Contractions induced in mesenteric arteries by noradrenaline (0.5-8 micromol/l) were comparable in lean and obese groups, but vasorelaxation in noradrenaline-preconstricted arteries was markedly reduced in dietary-obese rats of both sexes. Concentration-response curves to endothelium-dependent vasorelaxants (acetylcholine, A23187 and insulin) showed significant reductions in maximal relaxation (20-95% less than in leans; P<0.001) and significant rightward shifts in EC(40) (concentration giving 40% of maximal response) (P<0.01). Relaxation in response to the direct NO donor, sodium nitroprusside, showed a lesser impairment (12%; P<0.01) in dietary-obese rats. Maximal relaxation to acetylcholine was correlated inversely in both sexes with fat-pad mass (r(2)=0.37, P<0.05) and plasma triacylglycerols (r(2)=0.51, P<0.01), and with leptin in males only (r(2)=0.35, P<0.05). Independent determinants of acetylcholine-induced relaxation were fat mass and plasma triacylglycerols; plasma insulin and insulin sensitivity had no effect. Dietary-induced obesity severely impaired arterial relaxation in both sexes, particularly at the endothelial level. This is not attributable to insulin resistance, but may be related to moderate hypertriglyceridaemia.

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“…Firstly, rats with dietary-induced obesity -like the widely studied genetic models -show markedly impaired arterial relaxation, mainly due to endothelial dysfunction. Similar observations have also been reported previously implying an effect of gender on vascular contractility [25][26][27]. Our findings therefore throw new light on the causes of arterial disease in obesity, and also directly challenge the notion that vascular dysfunction in obesity is caused primarily by insulin resistance [3,13].…”

Section: Discussionsupporting

confidence: 90%

Dietary obesity in the rat induces endothelial dysfunction without causing insulin resistance: a possible role for triacylglycerols

Naderali

¹

,

Brown

²

,

Pickavance

³

et al. 2001

View full text Add to dashboard Cite

Impaired arterial vasorelaxation, due primarily to endothelial dysfunction, is associated with obesity. To clarify the relationship with insulin resistance and other metabolic disturbances, we studied endothelial-dependent and -independent vascular responses in rats with dietary-induced obesity. Dietary-obese rats had significantly higher body weights (10-32%; P<0.001) and fat-pad masses (220-280%; P<0.001) than lean controls, together with raised plasma levels of triacylglycerols (15-80%; P<0.001), non-esterified fatty acids (13-38%; P<0.05) and leptin (85-180%; P<0.001). However, measures of insulin sensitivity (including the hyperinsulinaemic-euglycaemic clamp in a parallel experiment) were comparable with those in controls. Contractions induced in mesenteric arteries by noradrenaline (0.5-8 micromol/l) were comparable in lean and obese groups, but vasorelaxation in noradrenaline-preconstricted arteries was markedly reduced in dietary-obese rats of both sexes. Concentration-response curves to endothelium-dependent vasorelaxants (acetylcholine, A23187 and insulin) showed significant reductions in maximal relaxation (20-95% less than in leans; P<0.001) and significant rightward shifts in EC(40) (concentration giving 40% of maximal response) (P<0.01). Relaxation in response to the direct NO donor, sodium nitroprusside, showed a lesser impairment (12%; P<0.01) in dietary-obese rats. Maximal relaxation to acetylcholine was correlated inversely in both sexes with fat-pad mass (r(2)=0.37, P<0.05) and plasma triacylglycerols (r(2)=0.51, P<0.01), and with leptin in males only (r(2)=0.35, P<0.05). Independent determinants of acetylcholine-induced relaxation were fat mass and plasma triacylglycerols; plasma insulin and insulin sensitivity had no effect. Dietary-induced obesity severely impaired arterial relaxation in both sexes, particularly at the endothelial level. This is not attributable to insulin resistance, but may be related to moderate hypertriglyceridaemia.

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“…E 2 improves coronary blood flow in both male and female spontaneously hypertensive rat, although the response is significantly greater in females (13). In contrast, E 2 -induced vasorelaxation is greater in mesenteric arteries from male guinea pigs (25). In denuded rat aortic rings, there is no sex difference in E 2 -induced vasodilation (9), and E 2 -induced vasorelaxation is independent of sex in rat tail arteries (10).…”

Section: Discussionmentioning

confidence: 91%

Reduced vasorelaxation to estradiol and G-1 in aged female and adult male rats is associated with GPR30 downregulation

Lindsey

¹

,

Silva

²

,

Silva

³

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Lindsey SH, da Silva AS, Silva MS, Chappell MC. Reduced vasorelaxation to estradiol and G-1 in aged female and adult male rats is associated with GPR30 downregulation. Am J Physiol Endocrinol Metab 305: E113-E118, 2013. First published May 14, 2013 doi:10.1152/ajpendo.00649.2012.-Previously, we reported that chronic activation of the estrogen receptor GPR30 by its selective agonist G-1 decreases blood pressure in ovariectomized hypertensive mRen2.Lewis (mRen2) rats but not intact male littermates. Furthermore, G-1 relaxes female mesenteric resistance arteries via both endothelium-dependent and -independent mechanisms. Because of the lack of a blood pressure-lowering effect by G-1 in males and the potential influence of aging on estrogen receptor expression, we hypothesized that GPR30-dependent vasodilation and receptor expression are altered in males and aged females. Thus, we assessed the response to 17␤-estradiol or G-1 in mesenteric arteries obtained from 15-wk-old normotensive Lewis and hypertensive mRen2 females and males as well as 52-wkold Lewis females. Vasodilation to 17␤-estradiol (E 2) and G-1 was significantly attenuated in 15-wk-old Lewis and mRen2 males compared with age-matched females. Pretreatment of male vessels with the nitric oxide synthase inhibitor L-NAME had no significant effect on the estradiol or G-1 response. In aged females, E 2 and G-1 vasorelaxation was also significantly blunted; however, L-NAME essentially abolished the response. Associated with the reduced vascular responses, GPR30 expression in mesenteric arteries was approximately 50% lower in males and aged females compared with young females. We conclude that alterations in GPR30 expression and signaling may contribute to vascular dysfunction in aging females and a greater blood pressure in hypertensive males.

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Vasorelaxant effects of oestradiols on guinea pigs: a role for gender differences

Cited by 9 publications

References 29 publications

Dietary obesity in the rat induces endothelial dysfunction without causing insulin resistance: a possible role for triacylglycerols

Dietary obesity in the rat induces endothelial dysfunction without causing insulin resistance: a possible role for triacylglycerols

Dietary obesity in the rat induces endothelial dysfunction without causing insulin resistance: a possible role for triacylglycerols

Reduced vasorelaxation to estradiol and G-1 in aged female and adult male rats is associated with GPR30 downregulation

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