Dose‐dependence and reversibility of the hemoconcentrating and hypotensive activities of atrial natriuretic peptide in binephrectomized rats

In addition to its blood pressure lowering effect, atrial natriuretic peptide (ANP) infusion, increases hematocrit and decreases plasma volume by inducing a transfer of plasma fluid from the vascular to the interstitial compartment. We explored the dose-dependence as well as the reversibility of these actions by measuring changes in mean arterial pressure (MAP), hematocrit and plasma protein concentration (PPC) in anesthetized acutely binephrectomized Sprague-Dawley rats. Infusion of ANP (10, 100 or 1000 ng/kg/min for 45 min) dose-dependently reduced MAP (+2.3 +/- 1.8, -5.8 +/- 2.5 and -8.6 +/- 1.3%) and increased hematocrit (1.7 +/- 0.4, 8.1 +/- 0.4 and 9.0 +/- 0.6%), corresponding to calculated decreases in plasma volume of 3.0 +/- 0.6, 13.1 +/- 0.6 and 14.4 +/- 0.9% respectively. PPC increased significantly less than expected for a plasma volume reduction without proteins extravasation indicating that some loss of plasma proteins occurred in response to ANP. Both the reduction in MAP and plasma volume were reversible within 45 min after discontinuation of ANP infusion. During the recovery period, PPC decreased to values lower than baseline suggesting that the hemodilution was not associated with a detectable return of proteins into the circulation. Thus, in binephrectomized rats, infusion of ANP induced a dose-dependent and reversible reduction in arterial pressure and plasma volume through an extrarenal mechanism. Moreover, ANP dose-dependently increased the vascular permeability to proteins; the escaped proteins remained out of the vascular space for at least the duration of the experiment (ie 45 min post-infusion).