A. Aging constitutes a risk factor in the development of cardiovascular disease. Older animals are more susceptible to vascular lesions after endothelial injury than are young animals. The mechanism leading to the increased proliferation of SMC in the intima is unknown. However, the intimal thickening may result from excessive production of growth factors and/or increasing the activities of proteinases known to enhance the degradation of the extracellular matrix components. The purpose of these studies was to examine the factors involved in the development of intimal thickening. Histological staining of the thoracic aorta with TGF-beta specific antibodies have revealed the presence of higher levels of extracellular TGFbeta1 in the basement membranes from old rats as compared to young. In contrast, no apparent age-related differences were detected in the levels of intracellular TGFbeta1 or extracellular TGFbeta2 and TGFbeta3. Significant elevations in collagenase activity were detected in aortic homogenates from old and balloon injured animals. These elevations may be involved in the degradation of matrix protein associated with SMC migration and intimal thickening. B. Age-related alterations in smooth muscle ion metabolism may contribute to the onset and progression of hypertension. A model for the investigation of this process involves freshly-isolated single rat arterial smooth muscle cells (SMC). These cells were used to investigate the relationship between intracellular [Ca2+] fluctuations and initial velocity of cell shortening induced by norepinephrine and K+ depolarization. The results showed that single cells retain a Ca2+- dependent variation in shortening velocity consistent with the behavior observed in multicellular (tissue) preparations.
