In postmenopausal women the mechanisms responsible for hypertension have not been completely elucidated, and there are no gender-specific guidelines for women despite studies showing that blood pressure is not as well controlled to goal in women as in men. In the present study we tested the hypotheses that the sympathetic nervous system and the renal sympathetic nerves contribute to hypertension in aging female rats, that sympathetic activation may be mediated by the melanocortin 3/4 receptor (MC3/4R), and that MC3/4R activation may be due to increases in leptin. α-1, β-1,2-Adrenergic blockade reduced blood pressure in both young (3-4 mo) and old (18-19 mo) female spontaneously hypertensive rats (SHR). Renal denervation attenuated the hypertension more in old females than young females. MC3/4R antagonism with SHU-9119 given intracerebroventricularly had no effect on blood pressure in either young or old females but significantly reduced blood pressure in old males. Plasma leptin levels were similar in old male and female SHR and in old versus young females. These data suggest that the hypertension in old female SHR is in part due to activation of the sympathetic nervous system, that the renal nerves contribute to the hypertension, and that the mechanism responsible for sympathetic activation in old females is independent of the MC3/4R.
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