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Effect of V1/V2-receptor antagonism on renal function and response to vasopressin in conscious dogs.

To characterize effects of V1- and V2-receptor stimulation on renal function, eight conscious mongrel female dogs were studied in four separate studies greater than or equal to 2 wk apart during the following six consecutive 20-min periods: 1) intrarenal administration of the full V1/V2-receptor antagonist SKF 105494 (100 ng.kg-1.min-1) during basal circulating vasopressin (VP) levels (n = 3), 2) elevation of renal arterial plasma VP concentrations by intrarenal administration of exogenous arginine VP (0.05 mU.kg-1.min-1, n = 5), 3) simultaneous administration of SKF 105494 at (100 ng.kg-1.min-1) with intrarenal administration of exogenous VP (0.05 mU.kg-1.min-1; n = 5), and 4) intrarenal vehicle alone (n = 5). When administered during conditions of basal circulating endogenous VP, the full receptor antagonist effects were limited to opposition of hydrosmotic effects of VP. Elevation of renal arterial plasma VP levels through infusion of exogenous VP resulted in decreased renal plasma flow, glomerular filtration rate, osmolar clearance, urinary flow rate, and free water clearance and increased urine osmolality. These effects were all abolished by simultaneous administration of V1/V2-receptor antagonist. These data suggest that, under basal low levels of circulating VP, VP only influences renal water excretion. However, when plasma VP concentrations are elevated, VP may contribute to renal vasoconstriction and secondarily to reduced solute excretion, in addition to its effects on free water clearance.