STRESS-INDUCED CHANGES OF GENE-EXPRESSION IN THE PARAVENTRICULAR NUCLEUS ARE ENHANCED IN SPONTANEOUSLY HYPERTENSIVE RATS

Heightened hypothalamic-pituitary-adrenal (HPA) axis responses have be en implicated in hypertension in the spontaneously hypertensive rat (S HR), but the exact mechanisms involved are poorly understood. To deter mine changes in gene expression in SHR in the paraventricular nucleus (PVN), stress-induced accumulation of CRF, CRF type 1 receptor (CRFR-1 ) genes, and immediate-early genes were examined using in situ hybridi zation in young (5 weeks old) and adult (12 weeks old) stroke-prone SH R (SHRSP), compared with normotensive Wistar Kyoto (WKY) rats. Restrai nt stress-induced accumulation of c-fos, jun B, and NGFI-B mRNA, and C RF hnRNA in the PVN was significantly higher in young and adult SHRSP than in WKY rats at 30 min, except for c-fos in young rats. CRFR-1 mRN A expression in the PVN was also significantly higher in adult SHRSP t han in WKY rats at 120 min after stress onset. GRF mRNA was increased in response to stress in young SHRSP. The basal CRF mRNA level in the PVN was significantly lower in adult SHRSP than in WKY rats. Young SHR SP exhibit greater ACTH responses to stress without significant change s in plasma corticosterone concentrations. The adult SHRSP exhibited l ower baseline concentrations of corticosterone and similar corticoster one response to stress with enhanced secretion of ACTH. Overall, these results demonstrated that stress-induced activation of immediate earl y genes and CRF gene transcription in the PVN, and ACTH secretion is e nhanced in early hypertensive, young, and adult SHRSP, suggesting that they are probably not the result of chronic alterations in blood pres sure. The abnormal hypothalamic-pituitary response to stress thus appe ars to be related to the development of hypertension.