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Stress‐Induced Changes of Gene Expression in the Paraventricular Nucleus are Enhanced in Spontaneously Hypertensive Rats
Author(s) -
Imaki Toshihiro,
Naruse Mitsuhide,
Harada Shoko,
Chikada Naoko,
Nakajima Kishiko,
Yoshimoto Takanobu,
Demura Hiroshi
Publication year - 1998
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1046/j.1365-2826.1998.00249.x
Subject(s) - medicine , endocrinology , corticosterone , in situ hybridization , spontaneously hypertensive rat , hypothalamus , basal (medicine) , messenger rna , gene expression , corticotropin releasing hormone , biology , chemistry , blood pressure , gene , hormone , biochemistry , insulin
Heightened hypothalamic‐pituitary‐adrenal (HPA) axis responses have been implicated in hypertension in the spontaneously hypertensive rat (SHR), but the exact mechanisms involved are poorly understood. To determine 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 hybridization in young (5 weeks old) and adult (12 weeks old) stroke‐prone SHR (SHRSP), compared with normotensive Wistar Kyoto (WKY) rats. Restraint stress‐induced accumulation of c‐ fos , jun B, and NGFI‐B mRNA, and CRF 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 mRNA expression in the PVN was also significantly higher in adult SHRSP than in WKY rats at 120 min after stress onset. CRF 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 SHRSP exhibit greater ACTH responses to stress without significant changes in plasma corticosterone concentrations. The adult SHRSP exhibited lower baseline concentrations of corticosterone and similar corticosterone response to stress with enhanced secretion of ACTH. Overall, these results demonstrated that stress‐induced activation of immediate early genes and CRF gene transcription in the PVN, and ACTH secretion is enhanced in early hypertensive, young, and adult SHRSP, suggesting that they are probably not the result of chronic alterations in blood pressure. The abnormal hypothalamic‐pituitary response to stress thus appears to be related to the development of hypertension.