Laboratory Investigation

Kidney International (1994) 46, 639–646; doi:10.1038/ki.1994.316

Renal vasoconstriction during inhibition of NO synthase: Effects of dietary salt

Xiaolin Deng1, William J Welch1 and Christopher S Wilcox1

1Division of Nephrology, Hypertension and Transplantation and Hypertension Center, University of Florida, College of Medicine and Veteran's Administration Medical Center, Gainesville, Florida, USA

Correspondence: Christopher S Wilcox MD PhD, Division of Nephrology and Hypertension, Georgetown University Medical Center, 3800 Reservoir Road NW, PHC F6003, Washington, D.C., 20007, USA.

Received 6 December 1993; Revised 13 April 1994; Accepted 14 April 1994.

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Abstract

Renal vasoconstriction during inhibition of NO synthase: Effects of dietary salt. Since dietary salt loading enhances nitric oxide (NO) generation in the kidney, we investigated the hypothesis that changes in salt intake have specific effects on vascular resistance in the kidney mediated by the L-arginine-NO pathway. We contrasted changes in renal and hindquarter vascular resistances (RVR and HQVR) in anesthetized rats during intravenous infusions of graded doses of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Groups (N = 8 to 10) of rats were 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 arterial pressure (DeltaMAP +32 plusminus 4 vs. +22 plusminus 3%; P = 0.05) and RVR (+160 plusminus 17 vs. +83 plusminus 10%; P < 0.005) and a greater fall in renal blood flow (DeltaRBF; -47 plusminus 3 vs. -32 plusminus 4%; P < 0.01); changes in 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 pressure (RPP) since it persisted in rats whose RPP was controlled by adjustment 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 activity in both HS and LS rats. After inhibition of ACE with captopril, or of angiotensin II type I (AT1) receptor with losartan, the increase in RVR with L-NAME remained greater in HS than LS rats. In conclusion, an increase in dietary salt potentiates the renal vascular response to L-NAME. This effect is specific for the kidney and cannot be ascribed to changes in NO responsiveness or RPP or to effects of Ang II generation or action on AT1 receptors.

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