Sodium excretion in response to vasopressin and selective vasopressin receptor antagonists.
The mechanisms by which arginine vasopressin (AVP) exerts its antidiuretic and pressor effects, via activation of V2 and V1a receptors, respectively, are relatively well understood, but the possible associated effects on sodium handling are a matter of controversy. In this study, normal conscious Wistar rats were acutely administered various doses of AVP, dDAVP (V2 agonist), furosemide, or the following selective non-peptide receptor antagonists SR121463A (V2 antagonist) or SR49059 (V1a antagonist). Urine flow and sodium excretion rates in the next 6 h were compared with basal values obtained on the previous day, after vehicle treatment, using each rat as its own control. The rate of sodium excretion decreased with V2 agonism and increased with V2 antagonism in a dose-dependent manner. However,for comparable increases in urine flow rate, the V2 antagonist induced a natriuresis 7-fold smaller than did furosemide. Vasopressin reduced sodium excretion at 1 mug/kg but increased it at doses >5 umg/kg,an effect that was abolished by the V1a antagonist. Combined V2 and V1a effects of endogenous vasopressin can be predicted to vary largely according to the respective levels of vasopressin in plasma,renal medulla (acting on interstitial cells), and urine (acting on V1a luminal receptors). In the usual range of regulation, antidiuretic effects of vasopressin may be associated with variable sodium retention. Although V2 antagonists are predominantly aquaretic, their possible effects on sodium excretion should not be neglected. In view of their proposed use in several human disorders, the respective influence of selective (V2) or mixed (V1a/V2) receptor antagonists on sodium handling in humans needs reevaluation.
Perucca
Julie
J
INSERM U 872, Université Paris Descartes, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France.
Bichet
Daniel G
DG
Bardoux
Pascale
P
Bouby
Nadine
N
Bankir
Lise
L
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000494:pharmacology* / Q000652:urine; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D004232:Diuretics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005665:Furosemide / Q000494:pharmacology; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000819:agonists*; D012964:Sodium / Q000652:urine*; D013141:Spiro Compounds / Q000494:pharmacology*; D014556:Urine
D065092:Antidiuretic Hormone Receptor Antagonists; D004232:Diuretics; D009025:Morpholines; D017483:Receptors, Vasopressin; D013141:Spiro Compounds; D001127:Arginine Vasopressin; D005665:Furosemide; D012964:Sodium; C103281:satavaptan; D003894:Deamino Arginine Vasopressin