Effect of immobilization stress on transcriptional activity of inducible immediate-early genes, corticotropin-releasing factor, its type 1 receptor, and enkephalin in the hypothalamus of borderline hypertensive rats.

The effects of immobilization on the expression of immediate-early gene c-fos and nerve growth factor-inducible (NGFI)-B mRNAs, corticotropin-releasing factor (CRF) mRNA, CRF heteronuclear RNA (hnRNA), CRF receptor types 1 and 2alpha mRNA, and enkephalin hn/mRNA were investigated in the hypothalamic paraventricular nucleus of Wistar-Kyoto (WKY) rats and borderline hypertensive rats (BHRs). Rats were deeply anesthetized 0, 30, 60, and 180 min after the beginning of the immobilization session (60 min maximum). BHR paraventricular nuclei displayed slight differences in their resting levels of NGFI-B mRNA and CRF hnRNA, both being significantly elevated compared with those of WKY rats. Conversely, basal levels of enkephalin primary transcript were significantly lower in BHRs. Immobilization, however, induced transient variations in the hybridization signals for all evaluated genes within the paraventricular nucleus (except for CRF 2alpha receptor). Immediate-early gene mRNA levels were higher and more prolonged in BHRs than in WKY rats. This heightened neuronal activation in the BHRs was associated with a more rapid increase in CRF mRNA expression (30 min) compared with that in WKY rats (60 min). It is interesting that a transient rise in CRF hnRNA levels was detected in stressed WKY rats, whereas the BHR group displayed a progressive decline in this transcript, being significantly below resting levels 180 min after the immobilization session. The stress-induced expression of CRF type 1 receptor mRNA was similar in both strains. Moreover, no significant differences were observed for enkephalin hn/mRNA in either strain during the immobilization session. Therefore, the hypothalamic paraventricular nucleus appears to be involved in the functional hyperreactivity of the hypothalamic-pituitary-adrenal and autonomic axes to stress observed in BHRs, which may lead ultimately to a stress-induced hypertensive state.