Selective blockade of oxytocin and vasopressin V(1a) receptors in anaesthetised rats: evidence that activation of oxytocin receptors rather than V(1a) receptors increases sodium excretion.
BACKGROUND
Although it is known that moderate-to-high doses of the neurohypophysial hormones oxytocin and vasopressin are natriuretic, doubts remain over the identity of the receptors responsible. To address this issue, we have used highly selective antagonists of oxytocin and vasopressin receptors in animals with elevated endogenous circulating levels of the 2 hormones.


METHODS
Rats were anaesthetised and prepared surgically for clearance studies, thereby raising plasma oxytocin and vasopressin concentrations. Sodium excretion, glomerular filtration rate and lithium clearance (an index of end-proximal fluid delivery) were measured: first during a control period, then after administration of the selective oxytocin receptor antagonist desGly-NH(2),d(CH(2))(5)[D-Trp(2),Thr(4),Dap(5)]OVT, the selective vasopressin V(1a) receptor antagonist d(CH(2))(5)[Tyr(Me)(2),Dab(5)]AVP, or vehicle alone.


RESULTS
Absolute and fractional sodium excretion fell in rats given the oxytocin antagonist (by 32 and 27%, respectively, compared with corresponding values in vehicle-infused rats), but not in those given the V(1a) antagonist or vehicle. Antinatriuresis was associated with a small reduction in the ratio of sodium clearance to lithium clearance (an index of the fraction of distally delivered sodium that escapes reabsorption in the distal nephron).


CONCLUSIONS
These results corroborate previous studies showing that activation of oxytocin receptors increases sodium excretion and imply that the natriuretic effect of elevated plasma vasopressin concentrations results from stimulation of oxytocin receptors.
Centre for Nephrology, University College London Medical School, London, UK. david.shirley@ucl.ac.uk
D G
DG
Shirley
M F
MF
Walter
B D
BD
Keeler
N J
NJ
Waters
S J
SJ
Walter
D000768:Anesthesia, General; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D008094:Lithium / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D009951:Ornipressin / Q000031:analogs & derivatives / Q000494:pharmacology; D010121:Oxytocin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000502:physiology*; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism* / Q000652:urine; D014667:Vasopressins / Q000097:blood
D065092:Antidiuretic Hormone Receptor Antagonists; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D014667:Vasopressins; D001127:Arginine Vasopressin; C074541:vasotocin, desGly(NH2)(9)d(CH2)5-Tyr(Me)(2)-Thr(4)-Orn(8)-; D009951:Ornipressin; D010121:Oxytocin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D008094:Lithium; D012964:Sodium