Differential Expression of AT 1 Receptors in the Pituitary and Adrenal Gland of SHR and WKY

Abstract

The renin-angiotensin (ANG) system has been implicated in the development of hypertension in spontaneously hypertensive rats (SHR). Because SHR are more susceptible to stress than normotensive Wistar-Kyoto rats (WKY), we measured the mRNA expression of AT 1A , AT 1B , and AT 2 receptors in the hypothalamo-pituitary-adrenal (stress) axis of male SHR in comparison to age-matched WKY at prehypertensive (3 to 4 weeks), developing (7 to 8 weeks), and established (12 to 13 weeks) stages of hypertension. AT 1A receptor mRNA was mainly expressed in the hypothalamus and adrenal gland. AT 1B receptor mRNA was detected in the pituitary and adrenal gland. AT 2 receptor mRNA was prominent only in the adrenal gland. When compared with WKY, SHR showed increased AT 1A receptor mRNA levels in the pituitary gland at all ages in contrast to reduced pituitary AT 1B receptor mRNA levels. In the adrenal gland of SHR, AT 1B receptor mRNA levels were decreased at the hypertensive stages when compared with WKY. The reduced expression of adrenal AT 1B receptor mRNA was localized selectively in the zona glomerulosa by in situ hybridization. No differences were observed between WKY and SHR in the expression of hypothalamic ANG receptors. ANG significantly increased plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone in dexamethasone-treated SHR but not in WKY. The aldosterone response to ANG was similar in SHR and WKY. Our results suggest a differential gene expression of AT 1A and AT 1B receptors in the hypothalamo-pituitary-adrenal axis of SHR and normotensive WKY and imply the participation of AT 1 receptors in an exaggerated endocrine stress response of SHR to ANG.