Propiedades farmacocinéticas y farmacodinámicas estereoselectivas de carvedilol y nebivolol en modelos de hipertensión experimental
The present thesis evaluated the pharmacokinetic/pharmacodynamic properties of the third generation b-blockers ?carvedilol and nebivolol- in spontaneously hypertensive (SH) rats, and animals treated with the nitric oxide synthase inhibitor L-NAME or with fructose. The rats received an intravenous do...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2015
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_873 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_873.dir/873.PDF |
| Aporte de: |
| Sumario: | The present thesis evaluated the pharmacokinetic/pharmacodynamic properties of the third generation b-blockers ?carvedilol and nebivolol- in spontaneously hypertensive (SH) rats, and animals treated with the nitric oxide synthase inhibitor L-NAME or with fructose. The rats received an intravenous dose of carvedilol and nebivolol determining the pharmacokinetic profile and the response on blood pressure and blood pressure variability. Carvedilol showed an enantioselective pharmacokinetic profile and a good relationship between plasma levels and cardiovascular response. Nebivolol also exhibited enantioselective pharmacokinetic behavior but a lack of pharmacokinetic/pharmacodynamic correlation for the hypotensive response. SH and LNAME rats showed increased hypotensive response to carvedilol and nebivolol suggesting a compromise of the vascular sympathetic system in the maintenance of the hypertensive state. On the other hand, the antihypertensive efficacy of both b blockers did not increase in fructose fed rats with regard to control animals demonstrating the absence of the participation of the vascular sympathetic system in the increase of blood pressure in this model. In comparison with the cardioselective b-blocker atenolol, carvedilol and nebivolol induced a greater reduction in central blood pressure and shortterm variability, suggesting an enhanced cardiovascular protection in the treatment of arterial hypertension. |
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