The aim of this study was to determine the possible influence of sex hormones on the contractile responses induced by clonidine, an agonist of α2-adrenoceptors, as well as the endothelial modulation of these responses. For this purpose, thoracic aorta segments from male (control and castrated) and female (in oestrous phase and ovariectomized) rats were used. In intact segments from the four groups of rats, clonidine (0.01-10 µmol/l) induced concentration-dependent contractions, which were increased by the nitric oxide synthase inhibitor Nω-nitro-⌊-arginine methyl ester (0.1 mmol/l) or by endothelium removal, but were reduced by 1 µmol/l yohimbine (an α2-adrenoceptor antagonist) in all animals and by 1 µmol/l indomethacin (a cyclo-oxygenase inhibitor) in control males only. The rank order of the magnitude of the maximal response was: oestrous females > ovariectomized females > control males > castrated males, whereas the sensitivity to clonidine (EC50 value) was similar in all animals. In endothelium-denuded segments, the rank order was: oestrous females = control males > ovariectomized females = castrated males. These results suggest that: (1) the presence of oestrogen or androgen increases the contraction caused by α2-adrenoceptor activation with clonidine; (2) endothelium negatively modulates the response to this agonist in the four groups of rats, due to endothelial NO release (entirely in females and in part in males); (3) androgen also seems to modulate the response by stimulating the release of an endothelial contracting factor, probably a prostanoid; and (4) the endothelium of males has a greater capacity than that of comparable females for negative regulation of the tension generated by the underlying vascular smooth muscle.
Gender differences in the endothelial regulation of α2-adrenoceptor-mediated contraction in the rat aorta
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Nuria TEJERA, Gloria BALFAGÓN, Jesús MARÍN, Mercedes FERRER; Gender differences in the endothelial regulation of α2-adrenoceptor-mediated contraction in the rat aorta. Clin Sci (Lond) 1 July 1999; 97 (1): 19–25. doi: https://doi.org/10.1042/cs0970019
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