N-acetyl cysteine attenuates ethanol induced hypertension in rats

All known pathways of ethanol metabolism result in the production of acetaldehyde, a highly reactive compound. N-acetyl cysteine, an analogue of the dietary amino acid cysteine, binds acetaldehyde, thus preventing its damaging effect on physiological proteins. This study examined the effect of oral N-acetyl cysteine on the increased blood pressure, platelet cytosolic free calcium, blood acetaldehyde and adverse renal vascular changes induced by chronic ethanol treatment in rats. Twenty-four male Wistar-Kyoto (WKY) rats, age 7 weeks were divided into four groups of six animals each. Animals in group I were given water and group II 5% ethanol in water for the next 14 weeks. Animals in group III were given 5% ethanol + 1% N-acetyl cysteine for 4 weeks followed by 5% ethanol + 2% N-acetyl cysteine for the next 10 weeks. Animals in group IV were given 5% ethanol for 7 weeks; at that time ethanol was withdrawn and animals were placed on water with 2% N-acetyl cysteine for the next 7 weeks. After 14 weeks systolic blood pressure and platelet cytosolic free calcium were all significantly higher (p<0.001) in rats given ethanol as compared to rats in other groups. N-acetyl cysteine treatment, along with ethanol, significantly (p<0.001) attenuated the increased blood pressure and platelet cytosolic free calcium and adverse renal vascular changes. Discontinuation of ethanol treatment for 7 weeks along with N-acetyl cysteine supplementation also significantly lowered the blood pressure and platelet cytosolic free calcium and attenuated adverse renal vascular changes. There was no significant difference in aortic malonaldehyde among four groups. Increase in blood acetaldehyde with ethanol treatment was significantly attenuated with N-acetyl cysteine treatment. These results suggest that acetaldehyde may be the cause of ethanol-induced hypertension and elevated cytosolic free calcium and renal vascular changes.