Mathis D R, Liu S S, Rodrigues B B, McNeill J H
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
Can J Physiol Pharmacol. 2000 Oct;78(10):791-8.
The effect of hypertension on the progression of diabetic cardiomyopathy was examined by attempting to induce a similar level of diabetes in both spontaneously hypertensive rats (SHR) and Wistar rats. Streptozotocin (STZ) was injected into SHR (45 mg/kg) and Wistar rats (55 mg/kg) before (eight weeks of age) and after (twelve weeks of age) the development of hypertension in the SHR. For both groups of animals, induction of diabetes resulted in depressed weight gain, increased food and fluid consumption, hypoinsulinemia, hyperglycemia, and hypertriglyceridemia. For the rats injected at eight weeks of age, an oral glucose tolerance test (OGTT) demonstrated that although the SHR were significantly less diabetic than Wistar rats, the degree of cardiac dysfunction was equivalent in both strains. These results suggest that hypertension was interacting with the diabetic condition to impair cardiac performance. Injecting SHR at twelve weeks of age increased the severity of diabetes but interestingly did not depress heart function compared with the non-diabetic SHR group. Injecting Wistar rats at this age also increased the severity of diabetes, but unlike the SHR diabetic animals, these rats still had impaired cardiac performance. These results suggest that hypertension exacerbates the cardiac dysfunction seen during diabetes, especially when SHR rats are injected with STZ prior to the elevation of blood pressure. Moreover, in the SHR, the development of LV hypertrophy at the time of STZ injection may have compensated for the damaging effects of diabetes on the myocardium, thereby enabling the heart to perform normally.
通过尝试在自发性高血压大鼠(SHR)和Wistar大鼠中诱导相似程度的糖尿病,研究了高血压对糖尿病性心肌病进展的影响。在SHR出现高血压之前(8周龄)和之后(12周龄),分别向SHR(45 mg/kg)和Wistar大鼠(55 mg/kg)注射链脲佐菌素(STZ)。对于两组动物,糖尿病的诱导均导致体重增加受抑、食物和液体摄入量增加、低胰岛素血症、高血糖和高甘油三酯血症。对于8周龄注射的大鼠,口服葡萄糖耐量试验(OGTT)表明,尽管SHR的糖尿病程度明显低于Wistar大鼠,但两种品系的心脏功能障碍程度相当。这些结果表明,高血压与糖尿病状态相互作用,损害心脏功能。12周龄时注射SHR会增加糖尿病的严重程度,但有趣的是,与非糖尿病SHR组相比,并未降低心脏功能。在此年龄注射Wistar大鼠也会增加糖尿病的严重程度,但与SHR糖尿病动物不同,这些大鼠的心脏功能仍然受损。这些结果表明,高血压会加剧糖尿病期间出现的心脏功能障碍,尤其是当SHR大鼠在血压升高之前注射STZ时。此外,在SHR中,注射STZ时左心室肥厚的发展可能补偿了糖尿病对心肌的损害作用,从而使心脏能够正常运作。