Hypertension and Stroke Mechanisms in Spontaneously Hypertensive Rats

Abstract

Since rats with spontaneous genetic hypertension were established, much progress has been made on the pathogenesis of hypertension. These models include genetically hypertensive rats of New Zealand strain (GH) 1958 (1), spontaneously hypertensive rats (SHR) 1963 (2), Lyon hypertensive strain (LH) 1973 (3), and Milan hypertensive strain (MH) 1974 (4). Dahl salt-sensitive (DS) rats 1962 (5) and Sabra hypertensive strain (SBH) 1972 (6) are rats that develop hypertension in response to excess sodium loading or DOCA-salt manipulation. These rats are now regarded as having somewhat different pathogenic factors from each other and can be utilized as models for essential hypertension in man, which is not a homogeneous disease entity, but rather primary hypertension probably caused by the different combination of etiologic factors. Among these models, SHR, which develop not only hypertension but also hypertensive complications, are superior to others that rarely develop cardiovascular diseases. Furthermore, stroke-prone SHR (SHRSP, 1974) (7) and arteriolipidosis-prone rats (ALR) 1977 (8), which were selectively bred from SHR, can develop cardiovascular diseases spontaneously or only by dietary manipulation, so that we can experimentally study not only the pathogenesis, but also the etiology and the prevention. Our studies have clarified that genetic predisposition and gene-environment interaction are important in the pathogenesis of these adult diseases. Therefore, there is a definite possibility that the predisposition of these diseases is detectable even at a young age, and that these cardiovascular diseases can be prevented by intervening pathogenic mechanisms through the control of environmental factors if prophylactic measures are started early enough (9).