Abnormalities in the hypothalamo-pituitary-adrenal axis in spontaneously hypertensive rats during development of hypertension.
Abnormalities in the hypothalamo-pituitary-adrenal axis in spontaneously hypertensive rats (SHR) during development of hypertension were investigated using in vivo and in vitro methods. Plasma ACTH responses to hemorrhage and ether stress were significantly smaller in 7-week-old SHR than in age-matched Wistar-Kyoto rats (WKY), while plasma corticosterone baseline levels and its response to stress were greater in SHR than in WKY. There was no significant difference in the plasma ACTH response to ether stress between bilaterally adrenalectomized SHR and WKY replaced with a 25% corticosterone pellet for 6 days. Adrenalectomy prevented the development of hypertension in SHR; however, corticosterone replacement restored hypertension. Plasma ACTH showed a smaller response to iv CRH injection in SHR than in WKY, while the ACTH response to arginine vasopressin was not different between SHR and WKY. CRH concentrations in the median eminence, posterior pituitary, and cerebral cortex were lower in SHR than in WKY, while the CRH concentration in the median eminence was not different in SHR and WKY when they were adrenalectomized with or without corticosterone replacement. Basal in vitro CRH release from hypothalamic tissue was reduced in SHR, while CRH release in response to 56 mM KCl was not different in SHR and WKY. These results suggest that adrenocortical function is enhanced in young SHR, that reduced ACTH response to stress and exogenous CRH in SHR may be ascribed to higher plasma corticosterone levels, and that corticosterone is essential for the development of hypertension in SHR.
Hashimoto
K
K
Third Department of Internal Medicine, Okayama University Medical School, Japan.
Makino
S
S
Hirasawa
R
R
Takao
T
T
Sugawara
M
M
Murakami
K
K
Ono
K
K
Ota
Z
Z
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001794:Blood Pressure; D001835:Body Weight; D003345:Corticosterone / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D006470:Hemorrhage / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology / Q000503:physiopathology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000502:physiology / Q000503:physiopathology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D011921:Rats, Inbred WKY / Q000502:physiology; D012016:Reference Values
D001127:Arginine Vasopressin; D011189:Potassium Chloride; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone