Estudio de las alteraciones vasculares (funcionales, bioquímicas y estructurales) inducidas por isquemia-reperfusión: Estrategias terapéuticas.

Hypertension is one of the main factors that contributes to the high incidence of cardiovascular diseases, among them cerebral ischaemia (CI). Both hypertension and CI are inflamatory diseases affected by arterial structural and functional changes. In a previous study we have observed that middle cerebral artery(MCA) ischemia-reperfusion (I/R) in normotensive (WKY) and spontaneously hypertensive (SHR) rats, infarct volume and interleukin-6 plasma levels were greater in SSHR rats. In addition, structural, myogenic mechanical and functional changes on MCA differed between strains suggesting that alteratios due to hypertension \i per se\i0 have a big influence on changes due to I/R. The results of our previous study seem to indicatethat the impaired capacity for cerebral blood flow autoregulation induced by chronic hypertension is involved in the poorer outcome of I/R in SHR rats. In addition, in the same study I/R increased the MCA the internal elastic laminae fenestra area. This effect could hypothetically facilitate the entry of a vasodilatador endothelial factor that would contribute to the observed decrease on the vascular myogenic tone observed in WKY protecting the brain from an increase of the cerebral blood flow and dimishing the infart volume. The \b main objective\b0 of this project is to deeply analyse the vascular alterations, not only functional but also biochemical and on vascular remodelling (cellular and whole tissue) observed after experimental focal ischaemia. For this purpose we will analyse the role of pre-existing alteratios due to hypertension using antihypertensive drugs that should normalize blood pressure and also the altered vascular parameter. These experiments will likely provide information that would help to understand the mechanisms that participate inthe greater infart volume hypertensive animals.