Hypertensive rats exhibit heightened expression of corticotropin-releasingfactor in activated central neurons in response to restraint stress

To test the hypothesis that chronically elevated sympathetic drive is assoc iated with hyperreactiveness of autonomic centers in the brain to stress, a dult spontaneously hypertensive rats (SHRs) and two strains of normotensive rats (Wistar Kyoto [WKY] and Sprague Dawley [SD] rats) were acutely expose d to restraint stress: controls from each strain were not stressed. Brain s ections were prepared for Fos immunohistochemistry to identify activated ne urons in the paraventricular nucleus of the hypothalamus, Barrington's nucl eus of the pans, nucleus of the tractus solitarius, and ventrolateral medul la, or for combined Fos immunohistochemistry and corticotropin-releasing fa ctor (CRF) in situ hybridization in the paraventricular nucleus and Barring ton's nucleus. Restraint led to increased activation of neurons in all nucl ei. Strain differences were found only in the caudal and rostral paraventri cular nucleus where restraint resulted in greater numbers of activated neur ons in SHRs compared to either normotensive strain. Levels of CRF mRNA in B arrington's nucleus of unrestrained rats were similar among strains. After restraint, mRNA levels and double labeled neurons were increased in Barring ton's nucleus of SHRs. In unstressed rats, CRF mRNA levels were elevated in some regions of the paraventricular nucleus in SHRs. After restraint, mRNA levels increased throughout the paraventricular nucleus of SHRs. Significa ntly greater numbers of double labeled neurons were found in the dorsolater al medial and ventral medial parvocellular paraventricular nucleus of stres sed SHRs compared to WKY or SD rats. These data show that chronic elevation in sympathetic activity, present in SHRs, is associated with hyperreactive ness of the paraventricular and Barrington's nucleus including recruitment of neurons to express CRF, and may have important implications for the resp onse of the hypothalamo-pituitary-adrenal axis during stress. (C) 1999 Else vier Science B.V. All rights reserved.