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2013, Número 4

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Rev Hosp Jua Mex 2013; 80 (4)


Posible mecanismo involucrado en el efecto vasodilatador inducido por fenproporex en anillos aórticos de rata

López-Canales JS, Lozano-Cuenca J, Morín-Zaragoza R, Rodríguez-Almaraz JE, López-Canales ÓA, Ruiz-Frutos C, Rodríguez CJD, Valencia-Hernández I

Idioma: Español
Referencias bibliográficas: 39
Paginas: 235-242
Archivo PDF: 210.67 Kb.


RESUMEN

El fenproporex, un fármaco supresor del hambre, induce relajación en anillos aórticos de rata precontraídos con fenilefrina; sin embargo, ningún estudio ha reportado los mecanismos involucrados en este efecto relajante. Por consiguiente, este estudio investigó los mecanismos involucrados en el efecto vasodilatador del fenproporex bajo condiciones experimentales diferentes (con o sin endotelio, y en la presencia o ausencia de diferentes bloqueadores/inhibidores). El fenproporex a concentraciones de 10-9-10-5 M indujo relajación dependiente de la concentración en los anillos aórticos de rata precontraídos con fenilefrina, los cuales: a) No se afectaron con 10-5 M de indometacina, 3.1 x 10-7 M de glibenclamida, 10-7 M de apamin o caribdotoxina 10-7 M. b) Significantemente atenuado por 10-5 M cicloheximida, 10-5 M L-NAME, 10-2 TEA y la combinación de caribdotoxina + apamin, y c) Bloqueada por la remoción del endotelio. Estos resultados sugieren que los efectos vasodilatadores del fenproporex en los anillos aórticos de rata precontraídos con fenilefrina, involucran la estimulación de mecanismos genómicos, liberación endotelial de óxido nítrico y estimulación de los canales de potasio de tipo Kv-, y en un menor grado canales de SKCa-, IKCa- y BKCa-.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Pagotto U, Vanuzzo D, Vicennati V, Pasquali R. Pharmacological therapy of obesity. G Ital Cardiol (Rome) 2008; 9: 83S-93S.

  2. Alemany M, Remesar X, Fernandez-Lopez JA. Drug strategies for the treatment of obesity. IDrugs: the investigational drugs journal 2003; 6: 566-72.

  3. Adams C, Cohen A. Appetite suppressants and heart valve disorders. Archives des maladies du coeur et des vaisseaux 1999; 92: 1213-9.

  4. Seghatol FF, Rigolin VH. Appetite suppressants and valvular heart disease. Current opinion in cardiology 2002; 17: 486-92.

  5. Scheen AJ. Sibutramine on cardiovascular outcome. Diabetes care 2011; 34(Suppl. 2): S114-S119.

  6. Subramanian S. Vollmer RR. Fenfluramine-induced hypothermia is associated with cutaneous dilation in conscious rats. Pharmacology, biochemistry, and behavior 2004; 77: 351-9.

  7. Ni W, Li MW, Thakali K, Fink GD, Watts SW. The fenfluramine metabolite (+)-norfenfluramine is vasoactive. The Journal of pharmacology and experimental therapeutics 2004; 309: 845-52.

  8. Ni W, Wilhelm CS, Bader M, Murphy DL, Lookingland K, Watts SW. (+)-Norfenfluramine-induced arterial contraction is not dependent on endogenous 5-hydroxytryptamine or 5- hydroxytryptamine transporter. The Journal of pharmacology and experimental therapeutics 2005; 314: 953-60.

  9. Hong Z, Olschewski A, Reeve HL, Nelson DP, Hong F, Weir EK. Nordexfenfluramine causes more severe pulmonary vasoconstriction than dexfenfluramine. American journal of physiology. Lung cellular and molecular physiology 2004; 286: L531-L538.

  10. Michelakis ED, Weir EK, Nelson DP, Reeve HL, Tolarova S, Archer SL. Dexfenfluramine elevates systemic blood pressure by inhibiting potassium currents in vascular smooth muscle cells. The Journal of pharmacology and experimental therapeutics 1999; 291: 1143-9.

  11. Woolard J, Bennett T, Dunn WR, Heal DJ, Aspley S, Gardiner SM. Acute cardiovascular effects of sibutramine in conscious rats. The Journal of pharmacology and experimental therapeutics 2004; 308: 1102-10.

  12. Comiran E, Souza DZ, Boehl PO, Cassia Mariotti K, Pechansky F, Duarte Pdo C, De Boni RB, Froehlich PE, Limberger RP. Fenproporex and amphetamine pharmacokinetics in oral fluid after controlled oral administration of fenproporex. Therapeutic drug monitoring 2012; 34: 545-53.

  13. Mariotti KC, Rossato LG, Froehlich PE, Limberger RP. Amphetamine-Type Medicines: A Review of Pharmacokinetics, Pharmacodynamics, and Toxicological Aspects. Current clinical pharmacology 2013.

  14. Zolkowska D, Rothman RB, Baumann MH. Amphetamine analogs increase plasma serotonin: implications for cardiac and pulmonary disease. The Journal of pharmacology and experimental therapeutics 2006; 318: 604-10. Rev Hosp Jua Mex 2013; 80(4): 235-242 López-Canales JS y cols. Efecto vasodilatador inducido por fenproporex. 241

  15. Animals (Scientific Procedures) Act 1986 (A(SP)A86).

  16. Steel RGD, Torrie JH. Principles and procedures of statistic: a biomedical approach. NY: McGraw-Hill; 1997.

  17. Palacios M, Knowles RG, Palmer RM, Moncada S. Nitric oxide from L-arginine stimulates the soluble guanylate cyclase in adrenal glands. Biochemical and biophysical research communications 1989; 165: 802-9.

  18. Mathie A, Wooltorton JR, Watkins CS. Voltage-activated potassium channels in mammalian neurons and their block by novel pharmacological agents. General pharmacology 1998; 30: 13-24.

  19. Romey G, Hugues M, Schmid-Antomarchi H, Lazdunski M. Apamin: a specific toxin to study a class of Ca2+- dependent K+ channels. Journal de physiologie 1984; 79: 259-64.

  20. Ouadid-Ahidouch H, Van Coppenolle F, Le Bourhis X, Belhaj A, Prevarskaya N. Potassium channels in rat prostate epithelial cells. FEBS letters 1999, 459: 15-21.

  21. Knot HJ, Nelson MT. Regulation of membrane potential and diameter by voltage-dependent K+ channels in rabbit myogenic cerebral arteries. The American journal of physiology 1995; 269: H348-H355.

  22. Leblanc, N., Wan, X., Leung, P.M., 1994. Physiological role of Ca(2+)-activated and voltage-dependent K+ currents in rabbit coronary myocytes. The American journal of physiology 266, C1523-1537.

  23. Moncada S, Higgs EA, Palmer RM. Characterization and biological significance of endothelium-derived relaxing factor. Biochemical Society transactions 1988; 16: 484-6.

  24. Moncada S, Palmer RM, Higgs EA. The discovery of nitric oxide as the endogenous nitrovasodilator. Hypertension 1988; 12: 365-72.

  25. Moncada S, Radomski MW, Palmer RM. Endothelium-derived relaxing factor. Identification as nitric oxide and role in the control of vascular tone and platelet function. Biochemical pharmacology 1988; 37: 2495-501.

  26. Nelson MT, Quayle JM. Physiological roles and properties of potassium channels in arterial smooth muscle. The American journal of physiology 1995; 268: C799-C822.

  27. Assis AC, Araujo IG, Lima RP, Almeida MM, Marinho AF, Barbosa-Filho JM, Cruz JS, et al. Warifteine, a bisbenzylisoquinoline alkaloid, induces relaxation by activating potassium channels in vascular myocytes. Clinical and experimental pharmacology & physiology 2013; 40: 37-44.

  28. Hoshi T, Wissuwa B, Tian Y, Tajima N, Xu R, Bauer M, Heinemann SH, et al. Omega-3 fatty acids lower blood pressure by directly activating large-conductance Ca(2)(+)- dependent K(+) channels. Proceedings of the National Academy of Sciences of the United States of America 2013; 110: 4816-21.

  29. Kang YH, Yang IJ, Morgan KG, Shin HM. Cinnamyl alcohol attenuates vasoconstriction by activation of K(+) channels via NO-cGMP-protein kinase G pathway and inhibition of Rho-kinase. Experimental & molecular medicine 2012; 44: 749-55.

  30. Wang TT, Zhou GH, Kho JH, Sun YY, Wen JF, Kang DG, Lee HS, et al. Vasorelaxant action of an ethylacetate fraction of Euphorbia humifusa involves NO-cGMP pathway and potassium channels. Journal of ethnopharmacology 2013.

  31. Wang Y, Han Y, Yang J, Wang Z, Liu L, Wang W, Zhou L, et al. Relaxant effect of all-trans-retinoic acid via NOsGC- cGMP pathway and calcium-activated potassium channels in rat mesenteric artery. American journal of physiology. Heart and circulatory physiology 2013b; 304: H51-H57.

  32. Xu YC, Leung GP, Wong PY, Vanhoutte PM, Man RY. Kaempferol stimulates large conductance Ca2+ -activated K+ (BKCa) channels in human umbilical vein endothelial cells via a cAMP/PKA-dependent pathway. British journal of pharmacology 2008; 154: 1247-53.

  33. Yamazaki F, Chi H, Eguchi S, Kawano T. Activation of ATP-sensitive potassium channels by nicorandil is preserved in aged vascular smooth muscle cells in rats. Journal of anesthesia 2013.

  34. Davies NW, Pettit AI, Agarwal R, Standen NB. The flickery block of ATP-dependent potassium channels of skeletal muscle by internal 4-aminopyridine. Pflugers Archiv: European journal of physiology 1991; 419: 25-31.

  35. Pataricza J, Marton Z, Lengyel C, Toth M, Papp JG, Varro A, Kun A. Potassium channels sensitive to combination of charybdotoxin and apamin regulate the tone of diabetic isolated canine coronary arteries. Acta Physiol (Oxf) 2008; 194: 35-43.

  36. Qiu Y, Quilley J. Apamin/charybdotoxin-sensitive endothelial K+ channels contribute to acetylcholineinduced, NO-dependent vasorelaxation of rat aorta. Medical science monitor: international medical journal of experimental and clinical research 2001; 7: 1129-36.

  37. Stankevicius E, Lopez-Valverde V, Rivera L, Hughes AD, Mulvany MJ, Simonsen U. Combination of Ca2+ -activated K+ channel blockers inhibits acetylcholine-evoked nitric oxide release in rat superior mesenteric artery. British journal of pharmacology 2006; 149: 560-72.

  38. Satav JG, Katyare SS, Fatterparker P, Sreenivasan A. Study of protein synthesis in rat liver mitochondria use of cycloheximide. European journal of biochemistry/FEBS 1977; 73: 287-96.

  39. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature: New biology 1971; 231: 232-5.




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