RENAL VASOCONSTRICTION DURING INHIBITION OF NO SYNTHASE - EFFECTS OF DIETARY SALT

Since dietary salt loading enhances nitric oxide (NO) generation in th e kidney, we investigated the hypothesis that changes in salt intake h ave specific effects on vascular resistance in the kidney mediated by the L-arginine-NO pathway. We contrasted changes in renal and hindquar ter vascular resistances (RVR and HQVR) in anesthetized rats during in travenous infusions of graded doses of the NO synthase inhibitor N-G-n itro-L-arginine methyl ester (L-NAME). Groups (N = 8 to 10) of rats we re maintained on a high salt (HS) or low salt (LS) diet for two weeks. Compared to those on LS, rats on HS had a greater increase in mean ar terial pressure (Delta MAP; +32 +/- 4 vs. +22 +/- 3%; P = 0.05) and RV R (+160 +/- 17 vs. +83 +/- 10%; P < 0.005) and a greater fall in renal blood flow (Delta RBF; -47 +/- 3 vs. -32 +/- 4%; P < 0.01); changes i n HQVR were similar in the two groups. The enhanced RVR response to L- NAME in HS rats could not be ascribed to the higher renal perfusion pr essure (RPP) since it persisted in rats whose RPP was controlled by ad justment of a suprarenal aortic clamp. Changes in RVR with an NO donor (SIN-1) were similar in HS and LS rats. L-NAME reduced plasma renin a ctivity in both HS and LS rats. After inhibition of ACE with captopril , or of angiotensin II type I (AT(1)) receptor with losartan, the incr ease in RVR with L-NAME remained greater in HS than LS rats. In conclu sion, an increase in dietary salt potentiates the renal vascular respo nse to L-NAME. This effect is specific for the kidney and cannot be as cribed to changes in NO responsiveness or RPP or to effects of Ang II generation or action on AT(1) receptors.