Mycophenolate mofetil prevents salt-sensitive hypertension resulting from nitric oxide synthesis inhibition

Recent studies have suggested that subtle microvascular and tubulointerstitial injury in the kidney can cause salt-sensitive hypertension. To test this hypothesis, we determined whether the mild renal disease induced by transient blockade of nitric oxide (NO) synthesis would result in salt-sensitive hypertension and whether prevention of the renal injury by coadministration of the immunosuppressive agent mycophenolate mofetil (MMF) would block the development of salt sensitivity.N ω-nitro-l-arginine-methyl ester (l-NAME; 70 mg/100 ml in the drinking water) was administered for 3 wk to rats with or without MMF (30 mg · kg−1 · day−1 by gastric gavage), followed by a 1-wk “washout” period in which the MMF was continued, which was followed in turn by placement on a high-salt (4% NaCl) diet for an additional 4 wk. Renal histology was examined at 3 and 8 wk, and blood pressure was measured serially.l-NAME treatment resulted in acute hypertension and the development of mild renal injury. During the washout perio...