Autonomic and cardiovascular effects of corticotropin-releasing factor in the spontaneously hypertensive rat

Abstract

Corticotropin-releasing factor (CRF) administered intracerebroventricularly (i.c.v.) produced a greater increase of plasma epinephrine and glucose concentrations in spontaneously hypertensive rats (SHR) than in Wistar-Kyoto (WKY) or Sprague-Dawley (SD) rats. In contrast, CRF given i.c.v. produced significant elevations of mean arterial pressure (MAP) and heart rate (HR) in WKY and SD rats, but not in SHRs. To determine whether the prominent rise of plasma epinephrine levels following CRF administration to SHRs was a unique response to this peptide, two other stimuli for epinephrine secretion were evaluated, i.e. bombesin given i.c.v., and insulin given intravenously (i.v.). In contrast to the apparent enhanced responsiveness of the SHR to CRF, plasma epinephrine levels following either bombesin or insulin administration were similar in SHR, WKY and SD rats. These results demonstrate that the adrenomedullary response to CRF administration in the SHR is of greater magnitude than in WKY or SD rats. In an effort to identify the mechanisms responsible for the differential cardiovascular and adrenomedullary responses to CRF in the SHR versus WKY rat, CRF binding studies were performed. No difference in binding affinity of [125I]CRF or CRF receptor number could be identified in brains from SHR and WKY rats. Thus, CRF influences cardiovascular and adrenomedullary functions in a qualitatively dissimilar fashion in SHR and WKY rats. These differences are not secondary to any measurable alteration in CRF receptor affinity and number in SHR and WKY rats.