Blunted renal responses to atrial natriuretic peptide and its reversal by unclipping in one-kidney, one clip Goldblatt hypertensive rats

Abstract

To evaluate the hypotensive and renal effects of atrial natriuretic peptide (ANP) in one-kidney, one clip Goldblatt hypertensive rats with and without renal arterial stenosis. The one-kidney, one clip hypertensive rats were divided into four groups: untreated time control, ANP-infused, unclipped and unclipped plus ANP-infused. The changes in blood pressure, glomerular filtration rate and renal excretory function were determined during intravenous vehicle and ANP infusions while the renal arterial clip was in place or removed acutely. One-kidney normotensive rats infused with ANP were used for comparison. In one-kidney control rats, ANP infusion at doses of 0.15, 0.30 and 0.45 microg/kg per min decreased the mean blood pressure from 121 +/- 4 to 108 +/- 5 (9%, P < 0.05), 104 +/- 5 (17%, P < 0.05) and 89 +/- 4 mmHg (25%, P < 0.05), respectively. There was no significant change in glomerular filtration rate. However, the absolute sodium excretion rate increased significantly, by 343 +/- 66, 770 +/- 91 and 786 +/- 78%, respectively. A comparable magnitude of increase in the fractional sodium excretion was noted. In one-kidney, one clip hypertensive rats, the similar three doses of ANP infusion reduced blood pressure from 179 +/- 7 to 162 +/- 8 (8%, P < 0.05), 146 +/- 9 (17%, P < 0.05) and 138 +/- 8 mmHg (22%, P < 0.05), respectively. A slight but insignificant increase in renal function was observed during ANP infusion. Removal of the renal arterial clip reduced blood pressure rapidly and caused a transient increase in renal function. Subsequent infusion of ANF further reduced blood pressure but increased sodium and water excretion markedly. There is a blunted natriuresis and diuresis in response to ANP infusion in one-kidney, one clip hypertensive rats. Surgical removal of the clip from the renal artery restores the natriuretic and diuretic effects of ANP.