Effect Of Nitric Oxide Synthase On Experimental Myocardial Ischemia/Reperfusion Model And Intervention By Amlodipine

Background and objective: Nitric oxide (NO), derived from the vascular endothelium or other cells of the cardiovascular system, has an important role in physiological regulation of blood flow and has pathophysiological functions in cardiovascular disease. We assessed the influence of amlodipine and cholesterol on NO and the expression of eNOS and iNOS in myocardial hR model in hypercholesterolemia rats. Methods: All studies were performed on 84 healthy male Wisatr rats, which were randomly divided into 5 groups as follows: 1, GC group (n16); 2, NC group (n=16); 3, AM group (n=16): Amlodipine (7.Smgkgd) during the last two weeks; 4, AL group (n= 16): Amlodipine (7.Smgkgd) + L-NAME (2Omg.kg~d) during the last two weeks; 5, Sham group (n~16): treated with dummy operation. Rats in GC group were fed with normal chow for 6 weeks. The rats of groups 2~ to 5~ were fed with 3~4% cholesterol and 1 5~2O% lard diet for 6 weeks. Groups 1st~4th were operated on hR model. The left coronaiy artery (LCA) was dissected thorax and ligated for 30 minutes, then followed a relaxation for 20 minutes or 2 hours, while the sham group had a bumbling ligation. MCP and HR were recorded, and serum NO concentration was detected. Then we observed the expression of iNOS and eNOS on endothelium of coronary vasculatures with high-SABC 3 technique. Rats from GC and HC groups were randomly picked out to for electron microscopic observation. Results: 1. Arnlodipine was given concomitantly to L-NAME significantly decreased HR (P<0.0l) but no influoence on MCP (P>0.05). 2. only moderate eNOS expressed on endothelium of coronary vasculatures in normal diet rats. Bioactivity of serum NO, expression of eNOS and iNOS on endothelium were upregulated, downregulated after ischemia 30 minutes, apparently increased after reperfusion 20 minutes, to the peak after reperfusion 2 hours in HG group. Compared with HG group, the effect was reversed partly by arnlodipine in AM group. In combined with L-.NAME, the effect of amlodipine on NO and eNOS and iNOS was partly prevented. 3. After high cholesterol-fed diet for 6 weeks, no atherogenesis was found in endothelium of thoracic aorta. C抩nclusions: 1. Bioactivity of NO and the expression of NOS on endothelium increased in hypercholesterolemia rats. Production of NO decreased and expression of eNOS and iNOS were downregulated significantly during ischemia. However, NO was produced and NQS was expressed increasingly in early reperfusion and reached the peak in lately. 2. The effect on NO and eNOS and iNOS induced by cholesterol was reversed partly by amlodipine. Amlodipine is effective on hypercholesterolemic, myocardial postischemic and early reperfusion damage reduction, and most probably nitric oxide plays a determinant role in this effect. 3. It is important to regulate the bioactivity of NO and the 4 expression of eNOS and iNOS due to their 揵i-side?effects on cardiovascular diseases.