Increased arginine vasopressin secretion may participate in the enhanced susceptibility of Lewis rats to inflammatory disease.
Lewis (LEW/N) and Fisher (F344/N) rats are histocompatible inbred strains characterized respectively by susceptibility and resistance to inflammatory disease. LEW/N rats have deficient corticotropin-releasing hormone (CRH), ACTH and corticosterone responses to inflammation, and increased circulating and hypothalamic concentrations of arginine vasopressin (AVP). CRH is produced locally at inflammatory sites, where it acts as a proinflammatory agent, while AVP has been reported to exert immunopotentiating effects in vivo and in vitro. In order to further investigate the mechanism of increased AVP secretion in LEW/N rats, we measured AVP and CRH mRNA in several hypothalamic nuclei in LEW/N and F344/N rats, using in situ hybridization histochemistry. LEW/N rats had increased AVP mRNA concentrations in the supraoptic (SON) and paraventricular (PVN), but not in the suprachiasmatic (SCN) nuclei. CRH mRNA, on the other hand, was decreased in the PVN of LEW/N rats. To examine the potential role of AVP and CRH in the exaggerated inflammatory responses of LEW/N rats, we pretreated young female Lewis and Fischer rats with AVP- and/or CRH-neutralizing rabbit antisera and elicited subsequently an inflammatory response by a nuchal subcutaneous injection of carrageenin. We demonstrated that both antisera decreased significantly the leukocyte concentration in the inflammatory exudate in LEW/N rats, but found no synergistic or addictive effects between them. We conclude that previously observed differences in hypothalamic AVP and CRH contents between LEW/N and F344/N rats correspond to differences in the steady state mRNA levels of the two neuropeptides and that both AVP and CRH participate in the excessive inflammatory response of Lewis rats as locally active proinflammatory agents.
Patchev
V K
VK
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
Mastorakos
G
G
Brady
L S
LS
Redwine
J
J
Wilder
R L
RL
Chrousos
G P
GP
D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D004198:Disease Susceptibility; D005260:Female; D007249:Inflammation / Q000503:physiopathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew
D012333:RNA, Messenger; D001127:Arginine Vasopressin; D003346:Corticotropin-Releasing Hormone