Predictive and preventive pathology of cardiovascular diseases

The development of genetic models for research on hypertension and stroke, spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP), have contributed not only to the elucidation of the pathogenesis of hypertension-related cardiovascular diseases (CVD) but also to their prediction and prevention. Since both genetic and environmental factors are involved in the pathogenesis of hypertension and stroke in SHR and SHRSP, the detection of the genetic factors and the control of environmental factors have been proven to be useful as predictive and preventive measures against hypertension and related CVD. Early rise in blood pressure, sympathetic overresponsiveness, early development of cardiovascular hypertrophy, increased salt-sensitivity and membrane abnormalities detected in vascular smooth muscle cells (VSMC) from SHR and SHRSP, which are related to the pathogenesis of hypertension, have been examined for their applicability to the prediction of hypertension in man. Pathogenic mechanisms of stroke in SHRSP have been studied by electron microscopy, and VSMC degeneration and necrosis were noted to start at the outer media of intracerebral arteries which were exposed to local hypoxia and hyponutrition due to limited diffusion through the blood-brain barrier. Macrophages are involved in the process of arterionecrosis with fibrin deposition in SHRSP, and their involvement has also been proven immunohistochemically in human autopsy cases. Moreover, reduction of regional cerebral blood flow, hypoxic vulnerability of the brain detected by the NMR technique and additional cellular abnormalities such as membrane fragility and accelerated lipid incorporation may possibly be applied to the prediction of stroke and atherosclerotic diseases in man. On the other hand, experimental control of cellular, neural and vascular mechanisms of hypertension and stroke in these animal models have been proven to be effective for the prevention of CVD not only pharmacologically but also non-pharmacologically by dietary sodium reduction, and increased intake of potassium, calcium, protein and dietary fiber. The applicability of dietary control of hypertension and stroke to humans has been supported by our epidemiological studies in Japan as well as by the WHO-coordinated international cooperative study on cardiovascular diseases and alimentary comparison (WHO CARDIAC study). These new experimental and epidemiological findings are extending new horizons in medicine, where the main medical activity should be focused on the prediction of diseases by detecting genetic disposition as well as on prevention by the control of environmental factors.