Samuel N Heyman1, Marina Goldfarb, Ahuva Shina, Fanny Karmeli, Seymor Rosen. 1. Department of Medicine, Hadassah University Hospital, Mt. Scopus and the Hebrew University Medical School, and Nephrology Unit, Bikur Holim Hospital, Jerusalem, Israel. Heyman@cc.huji.ac.il
Abstract
BACKGROUND: N-acetylcysteine (NAC) administration has been shown to ameliorate experimental acute renal failure induced by ischemia-reflow, and was found to prevent radiocontrast nephropathy in high-risk patients. While the protective effect of NAC has been primarily attributed to scavenging oxygen free radicals, improving renal microcirculation also may play a role in the prevention of acute renal failure. METHODS: This study was designed to explore the effect of NAC on renal microcirculation. Blood pressure, total renal blood flow and selective regional cortical and outer medullary blood flow were continuously monitored in anesthetized Sprague Dawley rats with ultrasonic and laser-Doppler probes during the infusion of NAC (60 mg/kg). RESULTS: In control intact rats blood pressure and renal microcirculation were unaffected by NAC. By contrast, following renal vasoconstriction induced by the radiocontrast agent iothalamate meglumine, NAC decreased total, cortical and medullary vascular resistance by 7 to 10% (P < 0.05). NAC also reduced renal vascular resistance by 16% when given during angiotensin II infusion (P < 0.05). Altered renal microcirculation, induced by the cyclooxygenase inhibitor indomethacin, by the nitric oxide synthase-inhibitor, Nomeganitro-l-arginine (L-NAME), or with their combination was partially restored by NAC. Nevertheless, NAC administration failed to attenuate renal function and morphology in a rat model of acute renal failure with selective outer medullary hypoxic injury, induced by indomethacin, L-NAME and iothalamate. CONCLUSIONS: NAC ameliorates renal vasoconstriction, an effect that seems to be mediated by mechanisms other than prostaglandins and nitric oxide. The potential renoprotective outcome of NAC and the role of its vasodilating effect on the pre-constricted renal vasculature should be evaluated further.
BACKGROUND:N-acetylcysteine (NAC) administration has been shown to ameliorate experimental acute renal failure induced by ischemia-reflow, and was found to prevent radiocontrast nephropathy in high-risk patients. While the protective effect of NAC has been primarily attributed to scavenging oxygen free radicals, improving renal microcirculation also may play a role in the prevention of acute renal failure. METHODS: This study was designed to explore the effect of NAC on renal microcirculation. Blood pressure, total renal blood flow and selective regional cortical and outer medullary blood flow were continuously monitored in anesthetized Sprague Dawley rats with ultrasonic and laser-Doppler probes during the infusion of NAC (60 mg/kg). RESULTS: In control intact rats blood pressure and renal microcirculation were unaffected by NAC. By contrast, following renal vasoconstriction induced by the radiocontrast agent iothalamate meglumine, NAC decreased total, cortical and medullary vascular resistance by 7 to 10% (P < 0.05). NAC also reduced renal vascular resistance by 16% when given during angiotensin II infusion (P < 0.05). Altered renal microcirculation, induced by the cyclooxygenase inhibitor indomethacin, by the nitric oxide synthase-inhibitor, Nomeganitro-l-arginine (L-NAME), or with their combination was partially restored by NAC. Nevertheless, NAC administration failed to attenuate renal function and morphology in a rat model of acute renal failure with selective outer medullary hypoxic injury, induced by indomethacin, L-NAME and iothalamate. CONCLUSIONS:NAC ameliorates renal vasoconstriction, an effect that seems to be mediated by mechanisms other than prostaglandins and nitric oxide. The potential renoprotective outcome of NAC and the role of its vasodilating effect on the pre-constricted renal vasculature should be evaluated further.
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