Overview: studies on spontaneous hypertension-development from animal models toward man

Abstract

The development of genetic rat models for research on hypertension, stroke and other cardiovascular diseases (CVD) such as spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) have contributed not only to the elucidation of the pathogenesis of hypertension-related CVD but also to their prediction and prevention. Since both genetic and environmental factors are involved in the pathogenesis of CVD as extensively studied so far on these models, the detection of the early pathogenic mechanisms related to the genetic factors and the control of environmental factors such as dietary improvement are useful as predictive and preventive measures against CVD. Sympathetic overresponsiveness, early development of cardiovascular hypertrophy, increased salt sensitivity and membrane or transport abnormalities in vascular smooth muscle cells (VSMC) from SHR and SHRSP, possibly related to the pathogenesis of hypertension, are so far regarded as predictors for hypertension partly applicable to human hypertension. Genetic pathogenic mechanisms of stroke in SHRSP which have been proven to be greatly influenced also by dietary factors are hypertension-induced VSMC degeneration and necrosis of intracerebral arteries due to local nutritional disturbance. One of predictors of stroke related to the pathogenic mechanisms is reduction of regional cerebral blood flow. On the other hand, the control of environmental factors, especially nutrition and diets such as intakes of animal and vegetable proteins, some amino acids and fatty acids, potassium, calcium, magnesium, dietary fibers, etc., have been experimentally demonstrated to be effective for the prevention of CVD in these genetic models, and the applicability of these experimental findings to the CVD prevention in man is now supported from our world-wide epidemiological studies (WHO CARDIAC Study).