Atrial natriuretic peptide and oxytocin induce natriuresis by release of cGMP.
Our hypothesis is that oxytocin (OT) causes natriuresis by activation of renal NO synthase that releases NO followed by cGMP that mediates the natriuresis. To test this hypothesis, an inhibitor of NO synthase, L-nitroarginine methyl ester (NAME), was injected into male rats. Blockade of NO release by NAME had no effect on natriuresis induced by atrial natriuretic peptide (ANP). This natriuresis presumably is caused by cGMP because ANP also activates guanylyl cyclase, which synthesizes cGMP from GTP. The 18-fold increase in sodium (Na+) excretion induced by OT (1 microgram) was accompanied by an increase in urinary cGMP and preceded by 20 min a 20-fold increase in NO3- excretion. NAME almost completely inhibited OT-induced natriuresis and increased NO3- excretion; however, when the dose of OT was increased 10-fold, a dose that markedly increases plasma ANP concentrations, NAME only partly inhibited the natriuresis. We conclude that the natriuretic action of OT is caused by a dual action: generation of NO leading to increased cGMP and at higher doses release of ANP that also releases cGMP. OT-induced natriuresis is caused mainly by decreased tubular Na+ reabsorption mediated by cGMP. In contrast to ANP that releases cGMP in the renal vessels and the tubules, OT acts on its receptors on NOergic cells demonstrated in the macula densa and proximal tubules to release cGMP that closes Na+ channels. Both ANP- and OT-induced kaliuresis also appear to be mediated by cGMP. We conclude that cGMP mediates natriuresis and kaliuresis induced by both ANP and OT.
Soares
T J
TJ
Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Coimbra
T M
TM
Martins
A R
AR
Pereira
A G
AG
Carnio
E C
EC
Branco
L G
LG
Albuquerque-Araujo
W I
WI
de Nucci
G
G
Favaretto
A L
AL
Gutkowska
J
J
McCann
S M
SM
Antunes-Rodrigues
J
J
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism* / Q000652:urine; D004231:Diuresis; D004573:Electrolytes; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009994:Osmolar Concentration; D010121:Oxytocin / Q000494:pharmacology*; D011188:Potassium / Q000652:urine; D051381:Rats; D017208:Rats, Wistar
D004573:Electrolytes; D010121:Oxytocin; D009320:Atrial Natriuretic Factor; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester