自然発症糖尿病ラット(WBN/Kob)における心筋障害とカテコラミン代謝に関する研究

Abstract

To clarify the relationship between cardiac involvement in diabetes and catecholamime metabolism, hearts of the male WBN/Kob rat, a new strain of spontaneously diabetic rat, were examined morphologically, and catecholamine concentration in cardiac tissue was measured. The heart in WBN/Kob rats showed focal myocytic necrosis and replacement fibrosis of the myocardium, and hypertrophy and dilatation in the left ventricle at the advanced stage. There were no significant morphological differences in the arteries and arterioles between WBN/Kob and control rats. In WBN/Kob rats, low catecholamine concentrations in cardiac tissue and high sensitivity of heart rate to catecholamine were present before the manifestation of diabetes, compared with control rats. To evaluate the effects of β blockade or angiotensin converting enzyme inhibitor on cardiovascular lesion, β blockade (metoprolol ; 0.4 mg/100 g BW/day) or ACE inhibitor (captopril ; 0.2 mg/100 g BW/day) was administrated to WBN/Kob rats for 18 months. In WBN/Kob rats treated with metoprolol and captopril, the systolic blood pressure was lower than that of controls (non-medicated WBN/Kob rats), and the heart weight as well as cross-sectional area of the vestricular wall were smaller than those of controls. In WBN/Kob rats treated with metoprolol, the degree of dilatation and fibrosis area of the left ventricle was diminished compared with that of other groups of rats. β blockade prevented the cardiovascular involvement in WBN/Kob rat from progression. The present study suggests that high sensitivity of cardiomyocyte to catecholamine may lead to cardiovascular involvements in diabetes mellitus.