The Effect Of Carvedilol And Different Doses Of Metoprolol On Atherosclerosis In Rabbits

Objective To study the effect of carvedilol and different doses of metoprolol onatherosclerosis in rabbits by testing their roles in releving oxidative damage, reducingatherosclerotic plaque and inhibiting the proliferation of vascular smooth muscle cells,besides, the antiatherosclrotic effects of the two kinds of drug are compared toprovide evidence for the clinical therapy.Methods Forty male New Zealand white rabbits were studied. The rabbits wererandomly devided into five groups: (1) normal group: normal diet (2) high-fat-dietgroup: high fat diet +immunologic injury (3) low-dose-metoprolol group: high fatdiet+immunologic injury+low dose metoprolol(10mg/kg) (4) large-dose-metoprololgroup: high fat diet+immunologic injury+large dose metoprolol(20mg/kg)(5)cavedilol group: high fat diet+immunologic injury +cavedilol(10mg/kg). Thecompounding of the high fat diet were: 1g cholesterol+5g lard+94g normal diet. Afterbeing fed for 10 weeks, all the rabbits were killed. The serum triglyceride andcholesterol were measuered by enzymic method, the serum SOD was measured byxanthine oxidative method, and the serum MDA was measured by thiobarbituric acidmethod. The aorta was harvested for the whole appearance view, and the ratio of thearea of the plaque to the aera of the whole intima were analysised. The expression ofthe PCAN and NF-κBp65 in aorta were measured by the method ofimmunohistochemistry.Results (1)Cmpared with the normal group the level of the serum trigiyceride andcholesterol in the high-fat-diet group, low-dose-metoprolol group, large-dose-metoprolol group and cavedilol group increased significantly(P＜0.01) but there wereno statistical differences among the four groups (P＞0.05). (2) In the high-fat-dietgroup, the level of serum SOD was lower and the level of serum MDA was higherthan those of the normal group(P＜0.01). Among the high-fat-diet group, low-dose- metoprolol group and large-dose-metoprolol group, the level of serum SOD and MDAshowed no statistical differences (P＞0.05), but in the cavedilol group, the level ofserum SOD increased and the level of serum MDA decreased compared with those ofthe high-fat-diet group, low-dose-metoprolol group and large-dose-metoprolol group(P＜0.01). (3) Cmpared with the normal group, the ratio of the area of the plaque to theaera of the whole intima increased obviousely in the high-fat-diet group (P＜0.01), butin the low-dose-metoprolol group, large-dose-metoprolol group and cavedilol group itdecreased sequencely compared with that of the high-fat-diet group (P＜0.01). (4)Cmpared with the normal group, the activity of the PCNA and NF-κBp65 waselevated in the high-fat-diet group (P＜0.01), but compared with the high-fat-diet groupthe activity was depressed in the low-dose-metoprolol group, large-dose-metoprololgroup and cavedilol group by turns (P＜0.01), besides, the expression of PCNA waspositively correlated with the expression of the NF-κBp65 in the plaque of theaorta(r=0.975, P＜0.01).Conclusion (1)High fat diet along with immunologic injury can induceatherosclerosis during which the peroxidation of the lipid and the proliferation ofvascular smooth muscle cells occur. (2)Metoprolol and carvedilol can reduce theatherosclerotic plaque and inhibit the proliferation of vascular smooth muscle cells;the effct of carvedilol is more obvious than that of metoprolol. (3)Metoprolol has noantioxidative effect while carvedilol can improve the oxidative damage significantlyin atherosclerosis. (4)Metoprolol and carvedilol have no influencement on lipidmetabolism; metoprolol shows dose dependent antiatherosclerotic feature andcarvedilol has a more excellent antiatherosclerotic effect than metoprolol.