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 blockade or potentiation (with N omega-nitro-L-arginine or N-acetyl-L-cysteine, respectively) modulates the systemic and renal responses to unclipping in anesthetized one-kidney, one-clip hypertensive rats (1K-1C). Cardiac output was measured by thermodilution. In time-control rats, mean 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), or renal plasma flow (RPF). Administration of N omega-nitro-L-arginine methyl ester (NAME, 10 micrograms/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, whereas TPR increased by 103%. Also, in rats given NAME, GFR and RPF decreased by 20% and 45%, respectively, at the end of the experiment. The effect of N-acetyl-L-cysteine (NAC, 300 mg/kg), a sulfhydryl group donor that may protect NO from free radical destruction by forming an S-nitrosothiol compound, was also evaluated. NAC potentiated the depressor response to unclipping (from 180 +/- 5 mm Hg to 97 +/- 3 mm Hg), and GFR and RPF increased by 80% and 35%, respectively. These effects of NAC appear to be NO dependent, as they were blocked by simultaneous administration of NAME. However, no significant differences were observed among groups in cumulative excretion of sodium and water, demonstrating that the hemodynamic effects of NAME and NAC after unclipping are due to mechanisms other than renal excretory changes. The results of the present study indicate that the cardiovascular depressor effects of unclipping are modulated by endothelium-derived nitric oxide.
Fenoy
F J
FJ
Departmento de Fisiología y Farmacología, Facultad de Medicina, Murcia, Spain.
Tornel
J
J
Madrid
M I
MI
López
E
E
García-Salom
G
G
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D000111:Acetylcysteine