Atrial natriuretic peptide (ANP) attenuates lipid peroxidation in anesthetized atherosclerotic male rabbits by reduction of renin-angotensin-aldosterone system (RAAS) activity
Konstantinos Kallaras1, Michael Karamouzis2, Vassiliki Stergiou-Michailidou1 & Thomas Zaraboukas3
Reactive oxygen species (ROS) are involved in the pathogenesis of atherosclerosis. Atrial natriuretic peptide (ANP) reduces thioredoxin in heart failure patients, whereas adrenomedullin, acting as an antioxidant, protects rat cardiomyocytes from infarction and mouse vascular smooth muscle cells from angiotensin II (AII) oxidative effect. Besides AII, aldosterone (Aldo) is also an activator of ROS. Aim of the study was the investigation of the eventual antioxidant effect of ANP on lipid peroxidation in male normal and cholesterol-fed (2% cholesterol-loaded feeding for 4 weeks) anesthetized (under urethane) New Zealand White rabbits. Blood samples for lipids, ANP, plasma renin activity (PRA), Aldo and 8-iso-prostaglandin-F2α (8-iso-PGF2α) were taken from cannulated right jugular vein. Rabbits were classified into two main groups: normal and hyperlipidemic. Each groups individuals were divided into two subgroups of five animals each. Blood samples for hormones measurement (by RIA) and 8-iso-PGF2α (by enzyme-immunoassay) were taken at 0 min and 20, 40, 60 min following an intravenous (iv) 20-min administration of either 0.2 μg/kg per min hANP in 5 ml normal saline or only 5 ml saline. Rings of ascending aorta were taken for histology. Mild to moderate atherosclerosis was found. The results, analyzed by paired t-test and repeated measures ANOVA, demonstrated that plasma 8-iso-PGF2α was reduced (P<0.05) at 40 and 60 min after ANP administration only in atherosclerotic rabbits. This reduction was coincident in these animals to a fall (P<0.05) of PRA at 20 min and Aldo at 40 and 60 min. There was a negative correlation between ANP and Aldo levels (r=− 0.28, P<0.01) and a positive correlation between Aldo and 8-iso-PGF2α (r=0.3, P<0.01). These results demonstrate that ANP (administered iv in a dose sufficient for achieving plasma levels 3fold the basal) attenuates lipid peroxidation in the presence of mild to moderate atherosclerosis, by reduction of RAAS activity.