Publication: Efectos cardiovasculares de una nueva dihidropiridina con propiedades paf-antagonistas
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2002
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Universidad Complutense de Madrid, Servicio de Publicaciones
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Abstract
El factor de activación plaquetaria o paf es un potente mediador inflamatorio de carácter fosfolipídico que esta implicado en una gran variedad de procesos fisiopatológicos. El desarrollo de potentes y selectivos antagonistas del receptor del paf ha proporcionado la posibilidad de analizar la participación real del paf en diferentes patologías y ha contribuido al tratamiento de enfermedades tales como asma, inflamación, isquemia y en diversos tipos de shock. Hemos analizado los efectos de una nueva dhp, el pca-4248, en diversas preparaciones cardiovasculares aisladas, en ratas normotensas e hipertensas anestesiadas y en tres modelos experimentales de shock. Nuestros resultados indican que esta dhp, a diferencia de nifedipino y nitrendipino, carece de acciones depresoras cardiacas, lo que indica que carece de propiedades bloqueantes de los canales de Ca. Además, es capaz de proteger y revertir los efectos del paf, asi como de producir efectos beneficiosos en diversos modelos de shock donde ya ha sido demostrada la implicación del paf. Por tanto, nuestros hallazgos sugieren que las acciones cardiovasculares del pca-4248 estarían relacionadas con su capacidad para antagonizar las acciones del paf
Platelet activation factor or paf is a powerful inflammatory mediator of a phospholipid nature that is involved in a wide variety of pathophysiological processes. The development of powerful and selective paf receptor antagonists has provided the possibility of analyzing the real participation of paf in different pathologies and has contributed to the treatment of diseases such as asthma, inflammation, ischemia and various types of shock. We have analyzed the effects of a new dhp, pca-4248, on various isolated cardiovascular preparations, on anesthetized normotensive and hypertensive rats and on three experimental models of shock. Our results indicate that this dhp, unlike nifedipine and nitrendipine, lacks cardiac depressant actions, indicating that it lacks Ca channel blocking properties. Furthermore, it is capable of protecting and reversing the effects of paf, as well as produce beneficial effects in various shock models where the involvement of paf has already been demonstrated. Therefore, our findings suggest that the cardiovascular actions of pca-4248 are related to its ability to antagonize the actions of paf
Platelet activation factor or paf is a powerful inflammatory mediator of a phospholipid nature that is involved in a wide variety of pathophysiological processes. The development of powerful and selective paf receptor antagonists has provided the possibility of analyzing the real participation of paf in different pathologies and has contributed to the treatment of diseases such as asthma, inflammation, ischemia and various types of shock. We have analyzed the effects of a new dhp, pca-4248, on various isolated cardiovascular preparations, on anesthetized normotensive and hypertensive rats and on three experimental models of shock. Our results indicate that this dhp, unlike nifedipine and nitrendipine, lacks cardiac depressant actions, indicating that it lacks Ca channel blocking properties. Furthermore, it is capable of protecting and reversing the effects of paf, as well as produce beneficial effects in various shock models where the involvement of paf has already been demonstrated. Therefore, our findings suggest that the cardiovascular actions of pca-4248 are related to its ability to antagonize the actions of paf
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Tesis de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Farmacología, leída el 10-12-1996