Hyponatremia in rats induces downregulation of vasopressin synthesis.
Hyponatremia due to inappropriate secretion of vasopressin is a common disorder in human pathophysiology, but vasopressin synthesis during hypoosmolality has not been investigated. We used a new method to quantitate synthesis of vasopressin in rats after 3, 7, and 14 d of hyponatremia induced by administering dDAVP (a vasopressin agonist) and a liquid diet. Vasopressin synthesis was completely turned off by 7 d. Vasopressin mRNA levels in the hypothalamus paralleled the reduction in synthesis and were reduced to levels of only 10-15% of the content in control rats. When hyponatremia was corrected by withdrawal of dDAVP, vasopressin mRNA slowly returned to normal over 7 d. The observation that vasopressin synthesis can be so completely turned off leads to several conclusions: under normal physiological conditions the neurohypophysis is chronically upregulated; there must be an osmotic threshold for initiation of vasopressin synthesis (and release); the large store of hormone in the posterior pituitary is essential for vasopressin to be available during times of decreased synthesis; and, finally, some nonosmolar stimulus for synthesis must be present during clinical disorders when vasopressin is secreted (and synthesized) despite hypoosmolality.
Department of Medicine, School of Medicine, University of Pittsburgh, Pennsylvania 15261.
A G
AG
Robinson
M M
MM
Roberts
W A
WA
Evron
J G
JG
Verbalis
T G
TG
Sherman
D000818:Animals; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D015536:Down-Regulation; D007010:Hyponatremia / Q000378:metabolism*; D008297:Male; D009481:Neurophysins / Q000096:biosynthesis / Q000235:genetics; D009994:Osmolar Concentration; D010121:Oxytocin / Q000096:biosynthesis / Q000235:genetics; D011311:Pressoreceptors / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000096:biosynthesis* / Q000235:genetics
D009481:Neurophysins; D012333:RNA, Messenger; D014667:Vasopressins; D010121:Oxytocin; D003894:Deamino Arginine Vasopressin