Control of the renal medullary circulation by vasopressin V1 and V2 receptors in the rat.

Utilization of the acute and chronically instrumented Sprague-Dawley rat model has provided new and informative data about the mechanisms of, and the role that circulating arginine vasopressin plays in, the regulation of blood flow to the renal medulla. Regional changes of blood flow were measured using implanted optical fibres and laser-Doppler flowmetry techniques. Transcriptional and translational sites of the V1a and V2 receptors were determined in microdissected intrarenal vascular segments from the cortex and medulla. Results from acute and chronic studies indicate the following. First, physiological elevations of plasma vasopressin concentration seen with 48 h of water restriction reduce blood flow to the inner medulla (via V1 receptors) while maintaining a constancy of blood flow to the outer medulla. Reduction of medullary blood flow is necessary to optimize urine osmolality during water restriction. Second, increases of plasma vasopressin concentration of as little as 8 pg ml(-1), which produce no change in baseline arterial pressure or renal cortical blood flow, can lower medullary blood flow selectively and greatly attenuate the arterial pressure-blood flow and pressure-natriuresis relationship. Third, medullary blood flow does not remain reduced in the face of sustained elevations of plasma vasopressin concentration, which appears to be related to the inability of vasopressin to produce a sustained hypertension. Fourth, V1a receptor mRNA and protein are present in the isolated cortical and medullary vasculature, but the V2 receptor mRNA and protein are found only in tubular segments. Levels of V2 receptor mRNA during water restriction were quantified using a competitive RT-PCR and a deletion mutant RNA transcript to control for the efficiency of the reaction, and Western blot analysis was utilized for quantification of the V2 receptor protein. The results demonstrated a time-dependent downregulation of the V2 receptor mRNA and protein within the rat kidney, specifically in the outer medulla. Fifth, the vasopressin-induced vasoconstriction of the medullary vasa recta microvessels was shown to be mediated via V1a receptors, and this response is normally modulated by vasopressin-stimulated release of nitric oxide (NO), via extravascular (presumably medullary collecting duct ) stimulation of V2 receptors. Finally, chronic vasopressin administration (10 days) increased nitric oxide synthase activity in the outer medulla and interstitial NO concentration in the medulla. These changes are essential to provide a constancy of blood flow to the renal medulla and buffer against the hypertensive actions of this potent vasoconstrictor peptide.