Interaction of acetaldehyde with plasma proteins of the renin-angiotensin system

Chronic alcohol abuse may lead to hypertension by stimulating the activity of the renin angiotensin system (RAS). While there are reports on the alcohol associated increase of angiotensin II in rats and increases of plasma renin activity in rats and human alcoholics, the exact mechanisms of stimulation of the RAS activity is not clear. This study provides evidence for a biochemical interaction of acetaldehyde, the primary oxidative metabolite of ethanol, upon bilaterally nephrectomized (NEPEX) rat plasma that contains significant quantities of angiotensinogen and lacks active renin. Rat plasma served as the source of renin in this study. Preincubation of NEPEX plasma with 0.2 M acetaldehyde at 4 degrees C for 2 h resulted in a 21% increase in the angiotensin I (A I) formation by the rat plasma renin and 27% increase in the A I formation by the trypsinized rat plasma renin. When the rat plasma which contains modest quantities of endogenous angiotensinogen in addition to renin was preincubated with 0.2 M acetaldehyde at 4 degrees C for 2 h, the rate of A I formation was increased by 10%. Equivalent amounts of ethanol did not modify the rate of A I generation when added to NEPEX plasma or rat plasma. These results suggest the possibility of a biochemical interaction of acetaldehyde with the renin substrate which may enhance the activity of the RAS cascade, thereby contributing to hypertension in chronic alcoholics.