Myocardial and vascular lesions in the LA/N-corpulent rat

Abstract

The LA/N-corpulent (LA/N-cp) rat is a normotensive strain derived from Koltesky's original mutant strain of the spontaneously hypertensive rat (SHR). When homozygous for the cp gene (cp/cp), the rats are hyperphagous, hyperlipidemic, hyperinsulinemic, and obese. The rats have been shown, by scanning electron microscope observation of the arterial system, to develop arterial lesions and occasional occlusive thrombi. These are significantly more frequent in the corpulent rats. Histological examination of the heart has shown the presence of four distinguishable types of lesions: type A, muscle scar or cell dropout with pigment deposition and inflammatory cell accumulation; type B, necrosis of a small number of myocytes with reactive inflammatory cells; type C, nodule of chronic inflammatory cells; type D, muscle scar without chronic inflammatory cells. Complete transverse sections of three regions of the heart were examined from rats 3, 6, and 9 months of age. Rats that were homozygous normal (+/+) showed an absence of all types of cardiac lesions. Male corpulent rats showed frequent lesions of all types with the frequency rising consistently with age. Female corpulent rats showed a similar incidence of types C and D lesions to males, but no type B lesions were found. Type A lesions, the most common in corpulent males, were found at a greatly reduced relative frequency. In some instances, we have found occlusive thrombi in a coronary artery of corpulent rats. The disease process in these animals occurs with a normal low fat, virtually cholesterol-free diet and no experimental manipulation.