Vasopressin does not mediate hypersensitivity of the hypothalamic pituitary adrenal axis during chronic stress.
The hypothesis that vasopressin (VP) becomes the main mediator of pituitary corticotroph responsiveness during chronic hypothalamic pituitary adrenal (HPA) axis activation was tested by examining the effect of pharmacologic VP receptor blockade on the adrenocorticotropic hormone (ACTH) and corticosterone responses of 14-day repeatedly restrained rats. In spite of the increased vasopressinergic activity, repeatedly restrained rats showed lower ACTH and corticosterone responses to 10 min white noise compared with handled controls. These responses were unchanged by injection of the nonpeptide-selective V1b receptor antagonist SSR149415 i.v., 1 h before noise application. In contrast to noise stress, plasma ACTH responses to i.p. hypertonic saline injection were enhanced in the repeatedly restrained rats compared with handled controls, but responses were also unaffected by SSR149415 administered orally, daily 1 h before restraint. Since SSR149415 effectiveness was low, we used minipump infusion of the peptide V1 receptor antagonist, dGly[Phaa1,D-tyr(et), Lys, Arg]VP (V1-Ant) for 14 days, which effectively blocked ACTH responses to exogenous VP. Chronic V1-Ant infusion reduced plasma ACTH responses to i.p. hypertonic saline in handled controls but not in repeatedly restrained rats. These data suggest that the increased vasopressinergic activity characteristic of chronic stress plays roles other than mediating the hypersensitivity of the HPA axis to a novel stress.
Chen
Jun
J
Section on Endocrine Physiology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892, USA.
Young
Sharla
S
Subburaju
Sivan
S
Sheppard
Jack
J
Kiss
Alexander
A
Atkinson
Helen
H
Wood
Susan
S
Lightman
Stafford
S
Serradeil-Le Gal
Claudine
C
Aguilera
Greti
G
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001835:Body Weight; D003345:Corticosterone / Q000097:blood; D004326:Drinking; D004435:Eating; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D007211:Indoles / Q000378:metabolism; D008297:Male; D009622:Noise; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011759:Pyrrolidines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000378:metabolism; D012149:Restraint, Physical; D013315:Stress, Psychological; D014667:Vasopressins / Q000378:metabolism*
C456029:1-(5-chloro-1-((2,4-dimethoxyphenyl)sulfonyl)-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl)-4-hydroxy-N,N-dimethyl-2-pyrrolidinecarboxamide; D065092:Antidiuretic Hormone Receptor Antagonists; D007211:Indoles; D011759:Pyrrolidines; D017483:Receptors, Vasopressin; D014667:Vasopressins; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone