Hypoxia of the arterial media has often been considered to be an etiologic factor in the production of various diseases of the arterial wall, such as dissecting aneurysm and atherosclerosis. Hypertension is a known risk factor for these diseases. In hypertension, there is thickening of the walls of large arteries. This may predispose arteries to hypoxia because of increased diffusional distances for oxygen and, possibly, an increase in total medial oxygen consumption. Changes in the amount and character of arterial wall lipids, glycosaminoglycans, and connective tissue have been stimulated by hypoxia in vitro. However, there are no in vivo studies of arterial wall oxygenation in hypertension as compared with loal histopathology. The hypothesis is that in vivo, after development of hypertension in miniature pigs, medial hypoxia precedes certain histopathologic changes.
The specific aims are to produce hypertension in miniature swine using the well defined unilateral nephrectomy/DOCA pellet implantation model; to study in vivo mural oxygenation of the proximal femoral artery using the microcathode technique after 0,2,4,8, and 16 weeks of hypertension; to quick freeze the corresponding tissue in vivo, and after sacrifice of the animals to use the tissue for evaluation of histologic and histochemical changes. The study will examine statistical correlations between oxygen levels and the appearance of specific histopathologic changes. In this way, it shall be determined if hypoxia, as related to normal oxygenation, occurs, and if it does, whether it precedes or follows histopathologic changes. The study is meant to add to knowledge of the fundamental mechanisms by which hypertension leads to clinically important vascular disease.
| Keegan, K; Johnson, D E; Williams, L T et al. (1991) Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3. Proc Natl Acad Sci U S A 88:1095-9 |
