PATHOPHYSIOLOGICAL DIFFERENCES BETWEEN OBESE AND NON-OBESE SPONTANEOUSLY HYPERTENSIVE RATS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 61  (2) , 195-207
Abstract
A genetic variant of the spontaneously hypertensive rat (SHR) was produced which becomes markedly obese and hypertensive; obese/SHR weigh 800 g vs. 300 g for nonobese cohorts. Serum enzymes creatine phosphokinase, serum glutamic oxaloacetic transaminase, glutamic pyruvate transaminase and lactate dehydrogenase are frequently abnormally elevated, concomitant with a high incidence of myocardial necrosis. Obese/SHR are hyperlipidemic with severe fatty infiltration of the liver; they are hyperglycemic with enormous islets of Langerhans and extensive .beta.-cell degranulation; despite elevated blood urea N (BUN) levels, they mainfest little or no damage. Measurement of corticosterone, deoxycorticosterone (DOC) and aldosterone in obese/SHR demonstrate marked hyper-responsiveness to moderate stress. Circulating prolactin levels are lower in obese and nonobese/SHR compared to SHR but obese/SHR manifest unusually high increases in circulating prolactin levels in response to stress. Obese/SHR are hyperinsulinemic and have subnormal growth-hormone levels. Despite mild hypertension, hyperglycemia and hyperlipidemia, obese/SHR show no evidence of atheromatous change but do develop early polyarteritis nodosa. The genetically programmed hypertension and hyperglycemia is mediated by increased DOC, aldosterone and corticosterone production, respectively; obesity, hypertension and diabetes in obese/SHR resemble human Cushing''s disease.