Primary Mechanisms for Novel Compound Pivanampeta Against Atherosclerosis in Rat and Rabbit Model of Atherosclerosis

Abstract

Abstract: Aim To investigate the anti-atherosclerotic mechanisms of the novel compound pivanampeta in the early and later stages of atherosclerosis evolution. Methods Rats or rabbits were randomly assigned to the control, the model and the pivanampeta-treated groups. The rats or rabbits in the model group and the pivanampeta-treated group were fed with hypercholesterol diet. The carotids of rabbits were cut into pieces and stained with HE.The rat or rabbit serum levels of TC, LDL-CHO, HDL-CHO, IL-8, ET-1, PGI2, TXA2, and NO were assayed. The expressions of MCP-1 and IL-8 mRNA on rabbit carotid were determined by semi-quantitative RT-PCR. Results Pivanampeta exerted an inhibitory effect on TXA2 formation without PGI2 production in the early and later stages of atherosclerosis. The significantly increased release of NO and the decreased release of IL-8 in the animals in pivanampeta-treated group were both detected in the rat atherosclerosis model. In the rabbit atherosclerosis model the expressions of IL-8 and MCP-1 mRNA in pivanampeta-treated group were decreased significantly.However, the treatment with pivanampeta had no effect on the levels of plasma cholesterol, MDA and SOD. Conclusion The increase of serum NO contents and the decrease of plasma TXA2 level, as well as its inhibition of expression of IL-8 and MCP-1 are probably involved in the mechanisms underlying the anti-atherosclerotic effects of pivanampeta.

Key words: atherosclerosis, atherosclerosis, nitric oxide, nitric oxide, PGI2, PGI2, TXA2, TXA2

CLC Number:

R963

R972.6

Supporting:

SHAN Li-mei, ZHANG Jin-chao, ZHAO Yan-ling, WANG Hai^*. Primary Mechanisms for Novel Compound Pivanampeta Against Atherosclerosis in Rat and Rabbit Model of Atherosclerosis[J]. .

References

[1] Fiscus RR. Molecular mechanisms of endothelium-mediated vasodilation [J]. Semin Thromb Hemost, 1988, 14 (Suppl): 12-22.
[2] Chester AH, O’Neil GS, Moncada S, et al. Low basal and stimulated release of nitric oxide in atherosclerotic epicardial coronary arteries [J]. Lancet, 1990, 336 (8720): 897-900.
[3] Creager MA, Cooke JP, Mendelsohn ME, et al. Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans [J]. J Clin Invest, 1990, 86 (1): 228-234.
[4] Shan LM, Wang H, Pharmacological characteristics of the endothelial target for acetylcholine induced vascular relaxation [J]. Life Sci, 2002, 70: 1285-1298.
[5] Braun M, Hohlfeld T, Kienbaum P, et al. Antiatherosclerotic effects of oral cicaprost in experimental hypercholesterolemia in rabbits [J]. Atherosclerosis, 1993, 103(1): 93-105.
[6] Kim SC, Choi IG, Oh CH, et al. Prostacyclin-to-thromboxane A2 ratio in arteriogenic impotence [J]. J Urol, 1990, 144 (6): 1373-1375.
[7] Jeremy RW, McCarron H, Sullivan D. Effects of dietary L-arginine on atherosclerosis and endothelium-dependent vasodilatation in the hypercholesterolemic rabbit [J]. Circulation, 1996, 94 (3): 498-506.
[8] Joris I, Zand T, Nunnari JJ, et al. Studies on the pathogenesis of atherosclerosis. I: Adhesion and emigration of mononuclear cells in the aorta of hypercholesterolemic rats [J]. Am J Pathol, 1983, 113 (3): 341-358.
[9] Lundahl J, Skold CM, Hallden G, et al. Monocyte and neutrophil adhesion to matrix proteins is selectively enhanced in the presence of inflammatory mediators [J]. Scand J Immunol, 1996, 44 (2): 143-149.
[10] Wang N, Tabas I, Winchester R, et al. Interleukin 8 is induced by cholesterol loading of macrophages and expressed by macrophage foam cells in human atheroma [J]. J Biol Chem, 1996, 271 (15): 8837-8842.
[11] Zeiher AM, Fisslthaler B, Schray-Utz B, et al. Nitric oxide modulates the expression of monocyte chemoattractant protein 1 in cultured human endothelial cells [J]. Circ Res, 1995, 76 (6): 980-986.
[12] Wung BS, Cheng JJ, Shyue SK, et al. NO modulates monocyte chemotactic protein-1 expression in endothelial cells under cyclic strain [J]. Arterioscler Thromb, 2001, 21 (12): 1941-1947.
[13] Boisvert WA, Santiago R, Curtiss LK, et al. A leukocyte homologue of the IL-8 receptor CXCR-2 mediates the accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice [J]. J Clin Invest, 1998, 101 (2): 353-363.