Vasorrelajación en la arteria pulmonar de rata inducida por timol monoterpeno: evaluación de la dependencia de los factores relajantes derivados del endotelio

Autores/as

DOI:

https://doi.org/10.33448/rsd-v10i4.13971

Palabras clave:

Arteria pulmonar; Vasorrelajación; Timol; Adenilil ciclasa; Canales de calcio dependientes del voltaje.

Resumen

Timol y carvacrol son los principales compuestos que se encuentran en el aceite esencial de Lippia mycrophylla (LM-OE) y tienen actividad espasmolítica. Este trabajo se desarrolló con el fin de explorar un posible efecto vasorrelajante de LM-OE y sus principales constituyentes en la arteria pulmonar de ratas. Para ello, el órgano se estimuló in vitro con fenilefrina (Phe) 3 mM y, en la contracción tónica, se añadieron de forma acumulativa LM-OE, carvacrol y timol, en ausencia o presencia de endotelio. Además, se evaluó el efecto relajante del timol en presencia de atropina, L-NAME, indometacina, 2,3-O-isopropilideno adenosina, H-89 e Y-27632. Además, los efectos del timol sobre las contracciones tónicas inducidas por KCl 30 u 80 mM y S-(-)-Bay K8644, así como su efecto inhibidor sobre las contracciones acumulativas inducidas por CaCl2. LM-OE, carvacrol y timol tuvieron efecto relajante sobre la arteria pulmonar, siendo timol el mas poderoso. Su potencia relajante en preparaciones con endotelio intacto se redujo con atropina, L-NAME, indometacina, 2,3-O-isopropilideno adenosina y H-89, sin alterar su máximo efecto relajante. Además, el monoterpeno relajó la arteria pulmonar precontraída por KCl 30 u 80 mM, antagonizó las contracciones acumulativas inducidas por CaCl2 y relajó el órgano precontraído por S-(-)-Bay K8644. Finalmente, el poder relajante del timol no fue modificado por Y-27632. Por tanto, el timol actúa mediante mecanismos dependientes e independientes del endotelio, posiblemente modulando positivamente la vía endotelial colinérgica, la liberación de prostanoides y la posterior activación de la vía AC/PKA, así como inhibiendo el influjo de Ca2+ por CaV.

Citas

Agra, M. F., Freitas, P. F., & Barbosa-Filho, J. M. (2007). Synopsis of the plants known as medicinal and poisonous in Northeast of Brazil. Revista Brasileira de Farmacognosia, 17, 114-140.

Alencar, A. K. N., Pereira, L. S., Silva, F. E. et al. (2013). A novel adenosine A2a receptor agonist attenuates the progression of monocrotaline-induced pulmonary hypertension in rats. Pulmonary & Respiratory Medicine, 4, 1-6.

Beer, A. M., Lukanov, J., & Sagorchev, P. (2007). Effect of Thymol on the spontaneous contractile activity of the smooth muscles. Phytomedicine, 14, 65-69.

Billington, C. K., & Hall, I. P. (2012). Novel cAMP signalling paradigms: therapeutic implications for airway disease. British Journal of Pharmacology, 166, 401-410.

Boskabady, M. H., Jafari, Z., & Pouraboli, I. (2011). The effect of carvacrol on muscarinic receptors of guinea‐pig tracheal chains. Phytotherapy Research, 25, 530-535.

Catterall, W. A. (2011). Structure and regulation of voltage-gated Ca2+ channels. Annual Review of Cell and Developmental Biology, 16, 521-555.

Chen, I. S., Dai, Z. K., Welsh, D. G. et al. (2011). Protein kinases modulate store-operated channels in pulmonary artery smooth muscle cells. Research Journal of Biological Sciences, 18, 1-12.

Choy, W. Y., Wong, Y. F., & Kwan, Y. W. (2002). Role of mitogen-activated protein kinase pathway in acetylcholine-mediated in vitro relaxation of rat pulmonary artery. European Journal of Pharmacology, 434, 55-64.

Clark, S. G., & Fuchs, L. C. (1997). Role of Nitric Oxide and Ca++-Dependent K+ Channels in Mediating Heterogeneous Microvascular Responses to Acetylcholine in Different Vascular Beds. Journal of Pharmacology and Experimental Therapeutics, 282, 1473–1479.

Dias-Junior, C. A., Cau, S. B. A., & Tanus-Santos, J. E. (2008). Papel do óxido nítrico na regulação da circulação pulmonar: implicações fisiológicas, fisiopatológicas e terapêuticas. Jornal Brasileiro de Pneumologia, 34, 412-419.

Furchgott, R. F., & Zawadzki, J. V. (1980). The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature, 288, 373–376.

Gao, Y., Portugal, A. D., Negash, S. et al. (2007). Role of Rho kinases in PKG-mediated relaxation of pulmonary arteries of etal lambs exposed to chronic high altitude hypoxia. American Journal of Physiology. Lung Cellular and Molecular Physiology, 292, 678–684.

Greyson, C. R. (2010). The Right Ventricle and Pulmonary Circulation: Basic Concepts. Revista Española de Cardiología, 63, 81-95.

Gurney, A. M. (1994). Mechanisms of drug-induced vasodilation. Journal of Pharmacy and Pharmacology, 46, 242-251.

Hall, I. P. (2000). Second messengers, ion channels and pharmacology of airway smooth muscle. European Respiratory Journal, 15, 1120–1127.

Huang, W., Yen, R. T., Mclaurine, M. et al. (1996). Morphometry of the human pulmonary vasculature. Journal of Applied Physiology, 81, 2123-2133.

Jeffery, T. K., & Wanstall, J. C. (2011). Pulmonary vascular remodeling in hypoxic rats: effects of amlodipine, alone and with perindopril. European Journal of Pharmacology, 416, 123–131.

Karasu-Minareci, E., Ozbudak, I. H., Ozbilim, G. et al. (2011). Acute Effects of Vardenafil on Pulmonary Artery Responsiveness in Pulmonary Hypertension. Scientific World Journal, 12, 1-6.

Knot, H. T., Brayden, E. J., & Nelson, M. T. (1996). Calcium channels and potassium channels. In: Bárány M (ed). Biochemistry of smooth muscle contraction. Elsevier Inc., 203-219.

Lau, E. M., Giannoulatou, E., Celermajer, D. S. et al. (2017). Epidemiology and treatment of pulmonary arterial hypertension. Nature Reviews Cardiology, 14, 603.

Magalhães, P. J., Lahlou, S., Jucá, D. M. et al. (2008). Vasorelaxation induced by the essential oil of Croton nepetaefolius and its constituents in rat aorta are partially mediated by the endothelium. Fundamental and Clinical Pharmacology, 22, 169-177.

Marques, A. J., & Filgueiras, C. A. L. (2009). O químico e o naturalista luso‑brasileiro Alexandre Antonio Vandelli. Quimica Nova, 32, 2492‑2500.

Moreira, F. V. (2013). Efeitos cardiovasculares do citral, monoterpenos majoritário do óleo essencial de Cymbopogon citratus, em ratos. Thesis (PhD in Health Sciences): Federal University of Sergipe.

Nagaoka, T., Morio, Y., Casanova, N. et al. (2004). Rho/Rho kinase signaling mediates increased basal pulmonary vascular tone in chronically hypoxic rats. American Journal of Physiology. Lung Cellular and Molecular Physiology, 287, 665–672.

Norel, X., Walch, L., Costantino, M. et al. (1996). M1 and M3 muscarinic receptors in human pulmonary arteries. British Journal of Pharmacology, 119, 149 157.

Pauvert, O., Lugnier, C., Keravis, T. et al. (2003). Effect of sildenafil on cyclic nucleotide phosphodiesterase activity, vascular tone and calcium signaling in rat pulmonary artery. British Journal of Pharmacology, 139, 513 522.

Peixoto-Neves, D., Silva-Alves, K. S., Gomes, M. D. M. et al. (2010). Vasorelaxant effects of the monoterpenic phenol isomers, carvacrol and thymol, on rat isolated aorta. Fundamental and Clinical Pharmacology, 24, 341–350.

Rees, D. D., Palmer, R. M. J., Schulz, R. et al. (1990). Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. British Journal of Pharmacology, 101, 746-752.

Ribeiro, T. P., Porto, D. L., Menezes, C. P. et al. (2010). Unravelling the cardiovascular effects induced by α-terpineol: A role for the nitric oxide-cGMP pathway. Clinical and Experimental Pharmacology and Physiology, 37, 811-816.

Rodrigues, F. F. G., Coutinho, H. D. M., Campos, A. R. et al. (2011). Antibacterial activity and chemical composition of essential oil Lippia microphylla Cham. Acta Scientiarum. Biological Sciences, 33, 141-144.

Rodríguez-Ramos, F., González-Andrade, M., & Navarrete, A. (2011). Gnaphaliin A and B relax smooth muscle of guinea-pig trachea and rat aorta via phosphodiesterase inhibition. Journal of Pharmacy and Pharmacology, 63, 926–935.

Ruan, C. H., Dixon, R. A. F., Willerson, J. T. et al. (2010). Prostacyclin Therapy for Pulmonary Arterial Hypertension. Texas Heart Institute Journal, 37, 391-399.

Sherwin, C. M., Christiansen, S. B., Duncan, I. J. et al. (2003). Guidelines for the ethical use of animals in applied ethology studies. Applied Animal Behaviour Science, 81, 291 305.

Singhal, S., Henderson, R., Horsfield, K. et al. (1973). Morphometry of the human pulmonary arterial tree. Circulation Research, 33, 190-197.

Sobolewski, A., Jourdan, K. B., Upton, P. D. et al. (2004). Mechanism of cicaprost-induced desensitization in rat pulmonary artery smooth muscle cells involves a PKA-mediated inhibition of adenylyl cyclase. American Journal of Physiology. Lung Cellular and Molecular Physiology, 287, 352–359.

Somlyo, A. P., & Somlyo, A. V. (2003). Ca2+ sensitivity of smooth muscle and non muscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiological Reviews, 83, 1325 1358.

Sommer, N., Ghofrani, H. A., Pak, O. et al. (2021). Current and future treatments of pulmonary arterial hypertension. British Journal of Pharmacology, 178, 6-30.

Subramani, J., Leo, M. D. M., & Kathirvel, K. (2010). Essential role of nitric oxide in sepsis-induced impairment of endothelium-derived hyperpolarizing factor-mediated relaxation in rat pulmonary artery. European Journal of Pharmacology, 630, 84-91.

Wang, Y., Gharahi, H., Grobbel, M. R. et al. (2021). Potential damage in pulmonary arterial hypertension: An experimental study of pressure‐induced damage of pulmonary artery. Journal of Biomedical Materials Research Part A, 109, 579–589.

Xavier, A. L., Pita, J. C. L. R., Brito, M. Y. et al. (2011). Chemical composition, antitumor activity, and toxicity of essential oil from the leaves of Lippia microphylla. Zeitschrift für Naturforschung, 70, 129 137.

Zahid, K. R., Raza, U., Chen, J. et al. (2020). Pathobiology of pulmonary artery hypertension: role of long non-coding RNAs. Cardiovascular research, 116, 1937-1947.

Zhang, S., Liu, Y., Guo, S. et al. (2010). Vasoactive intestinal polypeptide relaxes isolated rat pulmonary artery rings through two distinct mechanisms. Journal of Physiological Sciences, 60, 389–397.

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Publicado

11/04/2021

Cómo citar

SAMPAIO, R. de S. .; OLIVEIRA, G. A. de .; VASCONCELOS, L. H. C. .; FERREIRA, P. B. .; SILVA, M. da C. C. .; TAVARES, J. F. .; CAVALCANTE, F. de A. .; SILVA, B. A. da . Vasorrelajación en la arteria pulmonar de rata inducida por timol monoterpeno: evaluación de la dependencia de los factores relajantes derivados del endotelio. Research, Society and Development, [S. l.], v. 10, n. 4, p. e29010413971, 2021. DOI: 10.33448/rsd-v10i4.13971. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/13971. Acesso em: 8 ene. 2025.

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Ciencias de la salud