EFFECTS OF N-OMEGA-NITRO-L-ARGININE AND N-ACETYL-L-CYSTEINE ON THE REVERSAL OF ONE-KIDNEY, ONE-CLIP HYPERTENSION

The present study evaluated whether nitric oxide (NO) synthesis blocka de or potentiation (with N-omega-nitro-L-arginine or N-acetyl-L-cystei ne, respectively) modulates the systemic and renal responses to unclip ping in anesthetized one-kidney, one-clip hypertensive rats (1K-1C). C ardiac output was measured by thermodilution. In time-control rats, me an arterial pressure (MAP) decreased from 197 +/- 8 mm Hg to 139 +/- 4 mm Hg 3 h after unclipping, and cardiac index (CI) decreased by 35%, with a transient rise in sodium and water excretion and no changes in total peripheral resistance (TPR), glomerular filtration rate (GFR), o r renal plasma now (RPF). Administration of N-omega-nitro-L-arginine m ethyl ester (NAME, 10 mu g/kg/min) blunted the hypotensive (from 190 /- 6 mm Hg to 157 +/- 3 mm Hg), diuretic and natriuretic responses and potentiated the decrease in CI (40%) observed after unclipping, where as TPR increased by 103%. Also, in rats given NAME, GFR and RPF decrea sed by 20% and 45%, respectively, at the end of the experiment. The ef fect of N-acetyl-L-cysteine (NAG, 300 mg/kg), a sulfhydryl group donor that may protect NO from free radical destruction by forming an S-nit rosothiol compound, was also evaluated. NAC potentiated the depressor response to unclipping (from 180 +/- 5 mm Hg to 97 +/- 3 mm Hg), and G FR and RPF increased by 80% and 35%, respectively. These effects of NA C appear to be NO dependent, as they were blocked by simultaneous admi nistration of NAME. However, no significant differences were observed among groups in cumulative excretion of sodium and water, demonstratin g that the hemodynamic effects of NAME and NAC after unclipping are du e to mechanisms other than renal excretory changes. The results of the present study indicate that the cardiovascular depressor effects of u nclipping are modulated by endothelium-derived nitric oxide. (C) 1997 American Journal of Hypertension, Ltd.