The Cohen diabetic (non-insulin-dependent) hypertensive rat model. Description of the model and pathologic findings

The available diabetic hypertensive models are of type I chemically induced diabetes in one-clip Goldblatt rat or in the spontaneously hypertensive (SHR) rat. We describe here a genetic type II diabetic hypertensive model (CDHM) developed by cross breeding the Cohen diabetic rat (CDR) and the SHR. In the succeeding generations, sibling pairs with the highest spontaneous blood glucose (SBG) and blood pressure (BP) were selected and mated. In the sixth selected generation, non-insulin-dependent overt diabetes and hypertension were evident. Blood pressure was 171 +/- 1.2 mm Hg, spontaneous blood glucose 340 +/- 22 mg/dL, and plasma insulin at 60 min following intragastric (IG) glucose load 83.3 +/- 10.2 microU/mL. In the CDHM there was severe diffuse diabetic glomerulosclerosis and severe hypertensive changes in arteries and arterioles, characterized by fibrinoid necrosis and/or "onion skin" lesions, as well as by smooth muscle cell hyperplasia. Such vascular changes were not observed in the CDR or in the SHR. Myocardial changes were prominent, with foci of ischemic necrosis and hyperplastic vascular changes. This model may be useful in probing the mechanisms potentiating cardiovascular and renal morbid events in the setting of spontaneous hypertension and diabetes.