Effects of Estrogen on Nitric Oxide and Aortic Atherosclerosis in Cholesterol-Fed Rabbits

Yu, Jae Hyeon; Lee, Young; Yoon, Soo Young; Park, Sang Soon; Na, Myung Hoon; Lim, Seung Pyung; Lee, Chung Sik

Abstract

BACKGROUND: Although estrogen is known to retard atherosclerosis, the mechanisms of which remain unclear. To examine the effect of estrogen on blood nitric oxide production and aortic atherosclerosis, we did an experiment with rabbits. MATERIAL AND METHOD: Forty male New Zealand White rabbits aging 5 weeks were randomly divided as 10 normal diet(ND), 10 normal diet(ND) + transdermal estradiol-2 patches(END; 0.02 microgram/d), 10 hypercholesterol diet(CD ; 0.5% of diet; w/w), and 10 CD + transdermal estradiol-2 patches(ECD) group, respectively. After 12 weeks, we measured the serum estradiol-2, nitric oxide and cholesterol and examined the atherosclerotic lesion of thoracic and abdominal aorta with light and scanning electron microscopy. RESULT: The concentration of estradiol-2 was increased in both ED and ECD groups(p<0.001). The serum nitric oxide production of END, CD, and ECD groups decreased significantly than that of ND group(p<0.001). The total, HDL and LDL cholesterol concentrations were increase in both CD and ECD groups(p<0.001). Aortic lesion was observed only in CD and ECD groups, without any difference. On light microscopic examination, the lesions were consists mainly of accumulation of lipid-laden macrophages (foam cell). On scanning electron microscopic examinations, CD group showed scattered areas of endothelial damage. However, estradiol-2 administration to the cholesterol-fed animals did not significantly change these pathologic findings.
CONCLUSION
The results shows hyperlipidemia brings a decreased production of nitric oxide, probably due to endothelial dysfunction. Estradiol-2 patch administration decreased nitric oxide level in male cholesterol-fed rabbits with unknown mechanism. The transdermal estradiol-2 patch did not show any effect on blood cholesterol level. The estrogen did not cause any change on atherogenesis on both thoracic and abdominal aorta. The gender difference and administration method may offset the beneficial effect of estrogen on atherogenesis. To gain a complete understanding for the action of estrogen on atherogenesis, further detailed studies for both genders are needed.