N-acetylcysteine improves renal dysfunction, ameliorates kidney damage and decreases blood pressure in salt-sensitive hypertension

Background Salt-sensitive hypertension in humans and experimental animals causes progressive increases in renal damage and dysfunction. The Dahl salt-sensitive (S) rat closely mimics human salt-sensitive hypertension. Aim Our goal was to test the hypothesis that enhancing the glutathione system with dietary N-acetylcysteine administration in Dahl S rats on a high sodium intake for 5 weeks will attenuate the increases in arterial pressure, the decreases in renal hemodynamics and the increases in renal damage that normally occur in S rats on high sodium. Methods Forty-four 7- to 8-week-old Dahl S/Rapp strain rats were maintained on a high sodium (8%), high sodium + N-acetylcysteine (4 g/kg per day), or low sodium (0.3%) diet for 5 weeks. Rats had arterial and venous catheters implanted at day 21. Results By day 35 in the high-sodium rats, N-acetylcysteine treatment significantly increased the renal reduced-to-oxidized glutathione ratio, glomerular filtration rate, and renal plasma flow, and decreased renal cortical and medullary O-2(-) release, urinary protein excretion, renal tubulointerstitial damage and glomerular necrosis. At this time, mean arterial pressure increased to 183 +/- 1 mmHg, and N-acetylcysteine reduced this arterial pressure to 121 +/- 4 mmHg. By day 35 in S high-sodium rats, N-acetylcysteine had caused a 91% decrease in glomerular necrosis and an 83% decrease in tubulointerstitial damage. Conclusions In Dahl S rats on high sodium intake, arterial pressure increases significantly and renal injury is pronounced. Treatment with N-acetylcysteine enhances the renal glutathione system, improves renal dysfunction and markedly decreases arterial pressure and renal injury in Dahl salt-sensitive hypertension.