Feedback control of vasopressin and corticotrophin secretion in conscious dogs: effect of hypertonic saline.
Glucocorticoids are known to inhibit the ACTH response to a variety of stimuli. It has been suggested that vasopressin secretion is also inhibited by glucocorticoid negative feedback. The purpose of this study was to (1) determine the ACTH response to hypertonic saline and its sensitivity to glucocorticoid negative feedback and (2) to determine whether physiological elevations of plasma cortisol inhibit subsequent vasopressin responses to hypertonic saline. Five mongrel dogs (15-18 kg) were prepared with chronic arterial and venous catheters and studied while conscious. Ten experiments were performed on each dog in a randomized design separated by at least 5 days. Each experiment consisted of a pretreatment period (from -60 to -30 min except for dexamethasone administration) during which a glucocorticoid feedback signal was applied and a stimulus period (from 0 to 30 min) during which hypertonic saline was infused. The pretreatment and stimulus periods were separated by 30 min. Pretreatments were as follows: isotonic saline (control), half-maximal and maximal cortisol infusion (5.5 or 11 nmol/kg per min), ACTH(1-24) infusion (6.8 pmol/kg per min) which produces increases in endogenous cortisol, and dexamethasone (1.5 mg i.m.) given at 17.00 h the day before experimentation. Stimuli were as follows: hypertonic saline was infused at 0.2 or 0.4 mmol/kg per min which increased plasma sodium by about 6 or 12 mmol/l respectively. NaCl infusion at 0.2 mmol/kg per min had no effect on plasma ACTH or cortisol except when subsequent to ACTH(1-24) pretreatment when plasma ACTH actually increased to 41.4 +/- 2.9 pmol/l in response to hypertonic saline.(ABSTRACT TRUNCATED AT 250 WORDS)
Raff
H
H
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226.
Skelton
M M
MM
Cowley
A W
AW
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003907:Dexamethasone / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D005246:Feedback; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D012462:Saline Solution, Hypertonic; D012965:Sodium Chloride; D014667:Vasopressins / Q000378:metabolism*
D012462:Saline Solution, Hypertonic; D014667:Vasopressins; D012965:Sodium Chloride; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; C018038:dexamethasone acetate; D006854:Hydrocortisone