Natriuretic action of neurohypophysial peptides: effects of agonists and antagonists and implication of natriuretic receptor.
Neurohypophysial peptides possess natriuretic activity. Although it has been shown that the natriuretic action of these peptides can be dissociated from their antidiuretic activity (a V2-receptor mediated response), it is not known whether the V1-receptor or yet a third receptor type mediates the natriuretic response. Also, it has not been studied what effects V1- and V2-antagonists may have on urinary sodium excretion. To define this, we have studied the effects of four oxytocin (OT) agonists: arginine-vasopressin, OT, [Leu4]OT and [cyclo-Leu8]OT; two V1-receptor antagonists: [penicillamine1,Phe(Methyl)2,Thr4,Orn8]OT and [penicillamine1,D-Phe(Ethyl)2,Thr4,Orn8]OT and one V2-receptor antagonist: d-(CH2)5[D-Ile2,alpha-aminobutyric acid4]arginine-vasopressin on renal excretion of water and electrolytes in anesthetized rats under water diuresis. We also studied the effects of the antagonists on the OT-induced antidiuretic and natriuretic responses. Only the agonists, but not the antagonists, were found to have natriuretic activity. The natriuretic potency was not related to the peptide's antidiuretic activity, but was in the same rank order as their oxytocic activity (a V1-agonist effect). The effects of the antagonists on the OT-induced renal responses were studied at two dose levels, representing a strong and near maximal of their respective V1 and V2 inhibitory doses. The V1-antagonist had no effect on the antidiuretic response to OT but inhibited the natriuretic response in a dose-dependent manner. The antinatriuretic effect was also long-lasting as its antioxytocic activity. The V2-antagonist inhibited the antidiuretic response to OT in a dose-dependent manner but only the high dose inhibited the natriuretic response. These results indicate that the natriuretic action of OT was not mediated by V2-receptors and antinatriuresis was not specific for V1-antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
Chan
W Y
WY
Department of Pharmacology, Cornell University Medical College, New York, New York.
Hruby
V J
VJ
D000818:Animals; D007668:Kidney / Q000187:drug effects; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D010121:Oxytocin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology*; D017483:Receptors, Vasopressin; D014667:Vasopressins / Q000037:antagonists & inhibitors
D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D014667:Vasopressins; D010121:Oxytocin