Angiotensin II-induced hypertension differentially affects estrogen and progestin receptors in central autonomic regulatory areas of female rats.
Academic Article
Overview
abstract
Estrogen receptor (ER) activation in central autonomic nuclei modulates arterial blood pressure (ABP) and counteracts the deleterious effect of hypertension. We tested the hypothesis that hypertension, in turn, influences the expression and trafficking of gonadal steroid receptors in central cardiovascular circuits. Thus, we examined whether ER- and progestin receptor (PR)-immunoreactivity (ir) are altered in medullary and hypothalamic autonomic areas of cycling rats following chronic infusion of the hypertensive agent, angiotensin II (AngII). After 1 week AngII-infusion, systolic ABP was elevated from 103+/-4 to 172+/-8 mmHg (p<0.05; N=8/group) and all rats were in diestrus (low estrogen). In AngII-infused rats the number of PR-immunoreactive nuclei was reduced (-72%) compared to saline-infused controls also in diestrus (p<0.05). Furthermore, the intensity of ERalpha-ir increased selectively in nuclei (16%) and cytoplasm (21%) of cells in the commissural nucleus of the solitary tract (cNTS; p<0.05) while neither the number nor intensity of ERbeta-labeled cells changed (p>0.05). Following chronic AngII-infusion, electron microscopy showed a higher cytoplasmic-to-nuclear ratio of ERalpha-labeling selectively in tyrosine hydroxylase (TH)-labeled neurons in the cNTS. Furthermore, AngII-infusion increased ERalpha-ir in the cytosol of TH- and non-TH neuronal perikarya and increased the amount of ERalpha-ir associated with endoplasmic reticulum only in TH-containing perikarya. The data suggest that hypertension modulates the expression and subcellular distribution of ERalpha and PR in central autonomic regions involved in blood pressure control. Considering that ERalpha counteracts the central and peripheral effects of AngII, these receptor changes may underlie adaptive responses that protect females from the deleterious effects of hypertension.
