Chronic V2 vasopressin receptor stimulation increases basal blood pressure and exacerbates deoxycorticosterone acetate-salt hypertension.
The present study was intended to determine whether the long-term V2 receptor-mediated effects of vasopressin on sodium reabsorption in the renal collecting duct is an aggravating factor in salt-sensitive hypertension. Deoxycorticosterone acetate (DOCA)-salt hypertension was induced in uninephrectomized rats that had been chronically pretreated with a V2 agonist (dDAVP; 1-deamino-8D-arginine vasopressin; 0.6 microg/kg.d) or a V2 antagonist (SR121463, 3 mg/kg.d) or were untreated. Plasma osmolality and natremia were not significantly different in the groups. Blood pressure was significantly increased by dDAVP pretreatment (+11 mm Hg; P = 0.006), and this effect was exacerbated after DOCA-salt-induced hypertension (+17 mm Hg; P = 0.042). The dDAVP-treated rats had a lower hematocrit (40 +/- 2% vs. 47 +/- 1% and 45 +/- 2%) and markedly higher albuminuria (91 +/- 9 vs. 17 +/- 8 and 15 +/- 8 mg/d), mortality rate (50% vs. 0% and 0%), and cardiac and renal hypertrophy than the control and SR121463 groups. Histological renal lesions were worsened by V2 agonism and prevented by V2 antagonism. Renal mRNA expression of beta- and gamma-subunits of the epithelial sodium channel was significantly increased by dDAVP treatment (P < 0.05). These findings provide evidence that chronic stimulation of vasopressin V2 receptor raises basal blood pressure in rats and exacerbates the development of DOCA-salt hypertension, organ damage, and mortality. These effects could be due at least in part to the sustained stimulation of sodium reabsorption by epithelial sodium channel in the distal part of the nephron, which promotes sodium retention.
Fernandes
Sandrine
S
Institut National de la Santé et de la Recherche Médicale, Unité-367, Paris, France.
Bruneval
Patrick
P
Hagege
Albert
A
Heudes
Didier
D
Ghostine
Saïd
S
Bouby
Nadine
N
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001794:Blood Pressure / Q000187:drug effects*; D003900:Desoxycorticosterone; D004452:Echocardiography; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology*; D007668:Kidney / Q000502:physiology; D007672:Kidney Cortex / Q000378:metabolism; D007677:Kidney Function Tests; D008297:Male; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000819:agonists*; D012965:Sodium Chloride
D065092:Antidiuretic Hormone Receptor Antagonists; D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D003900:Desoxycorticosterone; D012965:Sodium Chloride