Mechanisms underlining gender differences in Phenylephrine contraction of normoglycaemic and short-term Streptozotocin-induced diabetic WKY rat aorta

Mechanisms underlining gender differences in Phenylephrine contraction of normoglycaemic and short-term Streptozotocin-induced diabetic WKY rat aorta
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DOI:
10.1016/j.vph.2011.11.009
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发表时间:
2012-09-01
影响因子:
4
通讯作者:
Mustafa, M. R.
Mustafa, M. R.
中科院分区:
医学2区
文献类型:
--
作者:
Aloysius, U. I.;Achike, F. I.;Mustafa, M. R.

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The female gender reduces the risk, but succumbs more to cardiovascular disease. The hypothesis that short-term (8 weeks) Streptozotocin-induced diabetes could produce greater female than male vascular tissue reactivity and the mechanistic basis were explored. Aortic ring responses to Phenylephrine were examined in age- and sex-matched normoglycaemic/diabetic rats. The normoglycaemic male tissue contracted significantly more than the normoglycaemic female and the male/female diabetic tissues. Endothelial-denudation. L-NAME or MB reversed these differences suggesting an EDNO-cGMP dependence. 17 beta-oestradiol exerted relaxant effect on all endothelium-denuded (and normoglycaemic endothelium-intact male) tissues, but not endothelium-intact normoglycaemic female. The greater male tissue contraction is attributable to absent 17 beta-oestradiol-modulated relaxation. Indomethacin blockade of COX attenuated male normoglycaemic and female diabetic tissue contraction (both reversed by L-NAME), but augmented diabetic male tissue contraction. These data are consistent with the raised contractile TXA(2) and PGE(2) in normoglycaemic male and diabetic female tissues, and the relaxant PGI(2) in diabetic male (and female). The higher levels of PGI(2) in the normoglycaemic and diabetic female perhaps explain their greater relaxant response to Acetylcholine compared to the respective male. In conclusion, there is an endothelium-dependent gender difference in the effect of short term diabetes on vascular tissue reactivity which is COX mediated. (C) 2011 Elsevier Inc. All rights reserved.