Evidence for the Involvement of Vasopressin in the Pathophysiology of Adriamycin-induced Nephropathy in Rats

Abstract

The effect of orally available, nonpeptide vasopressin V1 and V2 receptor antagonists on chronic progressive glomerular disease was investigated in Wistar rats with Adriamycin-induced nephropathy. At weeks 0 and 3, Adriamycin was injected twice, and at week 3 drugs started to be given as follows: groups 2 and 3 were treated with V1 and V2 antagonists, respectively, while the untreated group 1 served as control. To block the effects of vasopressin totally, both V1 and V2 antagonists were simultaneously administered (group 4). At weeks 8 and 10, V1 and V2 antagonists given either alone or combined significantly reduced the urinary protein excretion to the same levels. Urinary volume increased in groups 3 and 4 from week 4. Systolic blood pressure did not significantly increase in all groups during the study. Histological alterations in the kidney of groups 2, 3 and 4 were significantly attenuated compared to the control. These results suggest that both vasopressin V1 and V2 agonism plays a role in the pathophysiology of Adriamycin-induced nephropathy despite plasma levels of vasopressin within the normal range. These findings also lead to the notion that in some types of nephrotic patients these orally available V1 and/or V2 receptor antagonists may be effective for reduction in proteinuria and for retardation of progression of renal failure.

Increased Levels of Copeptin Before Clinical Diagnosis of Preeclampsia

“…23 Multiple animal studies suggest that vasopressin’s link with kidney function is causal 23 ; for instance, blocking vasopressin V1a or V2 receptors protects the deterioration of kidney function in rat models for nephropathy. 24, 25 Conversely, administration of desmopressin, a powerful V2-receptor agonist, in rats and humans increases GFR and urinary albumin excretion. 26 In our pregnancy observations, it would seem women with gestational hypertension (i.e., those who avoid kidney damage despite elevated blood pressure) do not overly secrete vasopressin above and beyond that of normal pregnancy.…”

Early, but not late therapy with a vasopressin V1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy

“…3 Variation in vasopressin levels could potentially lead to changes in renal function. 10,11 However, the late effects of a VRA when renal damage is already established are unknown. 4 By acting through V 1a -receptors, vasopressin causes contraction, proliferation and hypertrophy of the mesangial cells, [5][6][7] leading to a decrease in filtration rate and ultrafiltration coefficient.…”

Canine Model of Cardiorenal Failure

“…In dogs with CHF and RF, the values of AVP tended to be higher significantly than those in dogs with CHF, suggesting that the role of AVP in cardiorenal function might be more potent than in dogs with CHF. However, because a special role for AVP was reported in patients and experimental animals with RF [16][17][18], further investigations using V1 and V2 antagonists are needed to clarify the role of AVP in cardiorenal syndrome. The sympathetic nervous system is initially activated in CHF by the baroreflex sensors to provide inotropic support and preserve cardiac output.…”