Homocysteine potentiates esterase-induced contraction on rat aorta in vitro: A risk factor for atherosclerosis

Bu çalışmada, homosistein etkisi altında N-α- l-tosil arginin metil ester (TAME) ile arttırılmış sıçan thoracic aortunda in vitro kasılmayı nasıl etkilediği araştırılmıştır. Aort izole edilerek Krebs çözeltisi içeren bir organ banyosuna yerleştirilmiştir. Değişik konsantrasyonlarda $(10^{-15}-10^{-1}M)$ TAME çözeltisinde kesik aort stripleri test edilmiştir. TAME etki ettirilmiş bu striplerde ayrıca homosistein etkisi araştırılmıştır. Bulunan sonuçlara göre konsantrasyona bağlı TAME etkili kasılmanın önceden homosistein ile inkübe edilen striplerde görülen kasılmaya göre daha göze çarpıcı olduğu saptanmıştır.

Homosisteinin sıçan aortunda esteraz ile arttırılan in vitro kasılmayı güçlendirmesi: Athereosclerosis oluşumu için bir risk faktörü

The present study was designed to investigate the effect of homocysteine on N-α- l-tosyl arginine methyl esterinduced contraction of rat thoracic aorta in vitro. Aorta was isolated and mounted in an organ bath containing Krebs solution. The effect of TAME was tested on intact aortic strips by challenging with different concentrations of TAME $(10^{-15}-10^{-1}M)$ . The effects of homocysteine were also investigated on TAME-induced contraction on rat aorta strips. Our data showed that the concentration dependent TAME-induced contraction were more prominent when rat aortic strips were pre-incubated with homocysteine.

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  • Boushey CJ, Beresford SA, Omenn GS and Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA, 274: 1049-57, 1995.
  • Furchgott RF and Zawadski JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle. Nature. 288: 373-376, 1980.
  • Gurib FBH and Subratty AH. Involvement of Kinin Kallikrein and Prostaglandin in TAME-esterase induced contractions of rat aorta in vitro. Univ of Maur Res Journ. (in pres) 2002.
  • Gurib FBH and Subratty AH. Calcium antagonists improve TAME-esterase blunted endothelial-dependent relaxation. Indian J Pharmacol. 33: 384-385, 2001.
  • Guttormsen AB, Refsum H and Ueland PM. The interaction between nitrous oxide and cobalamin. Biochemical effects and clinical consequences. Acta Anaesthesiol Scand. 38: 753-6, 1994.
  • Lee ME and Wang H. Homocysteine and hypomethylation. A novel link to vascular disease. Trends Cardiovasc Med. 9: 49-54, 1999.
  • Lefer AM and Lefer DJ. The role of nitric oxide and cell adhesion molecules on the microcirculation in ischemia-reperfusion. Cardiovasc Res. 32: 743-752, 1996.
  • Lentz SR, Sobey CG, Piegors DJ, Bhopatkar MY, Faraci FM, Malinow MR and Heistad DD. Vascular dysfunction in monkeys with diet-induced hyperhomocyst(e)inemia. J Clin Invest. 98: 1 24-9, 1996.
  • McCully KS. Homocysteine and vascular disease. Nat Med. 2: 386-9,1996.
  • Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M and Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease. Engl J Med. 337: 4 230-6, 1997.
  • Stamler JS, Osborne JA, Jaraki O, Rabbani LE, Mullins M, Singel D and Loscalzo J. Adverse vascular effects of homocysteine are modulated by endothelial-derived relaxing factor and related oxides of nitrogen. J Clin Invest. 91: 1 308-18, 1993.
  • Schlaich MP, John S, Jacobi J, Lackner KJ and Schmieder RE. Mildly elevated homocysteine concentrations impair endothelial dependent vasodilation in hypercholesterolemic patients. Atheroscler. 153: 383-9, 2000.
  • Stampfer MJ and Malinow MR. Can lowering homocysteine levels reduce cardiovascular risk? N Engl J Med. 332: 328-9, 1995.
  • Stuhlinger MC, Tsao PS, Her JH, Kimoto M, Balint RF and Cooke JP. Homocysteine impairs the nitric oxide synthase pathway: Role of asymmetric dimethylarginine. Circulation. 21: 2569-75, 2001.
  • Subratty AH and Hossany R. Does TAME induced contraction involve an endothelial dependent nitric oxide-cyclic GMP mediated pathway? Indian J Exp Biol. 37: 406, 1999.
  • Subratty AH and Moonsamy J. Is TAME a potent constrictor of non-airway smooth muscles? Indian J Exp Biol. 36: 618, 1998.
  • Subratty AH, Mooradun A and Jowaheer V. TAME-esterase. A new cardiovascular risk factor in smokers. Indian J Exp Biol. 38: 610, 2000.
  • Tawakol A, Omland T, Gerhard M, Wu JT and Creager MA. Hyperhomocyst(e)inemia is associated with impaired endothelial-dependent vasodilation in humans. Circulation. 95: 5 1119-21, 1997.