Endoplasmic reticulum stress caused by left ventricular hypertrophy in rats: effects of telmisartan

Studies have revealed that excessive endoplasmic reticulum (ER) stress leads to apoptosis. Although cardiomyocytes apoptosis contributes to the transition from left ventricular hypertrophy (LVH) to heart failure, it is unknown whether ER stress participates in the pathologic process. The authors first induced coarctation of the abdominal aorta in rats to induce LVH and then investigated the effect of telmisartan on the resulting ER stress.

Male Sprague-Dawley rats were randomly divided into 3 groups: sham operation, abdominal aortic coarctation (AAC) and AAC + telmisartan. Telmisartan (5 mg · kg · d) or vehicle was infused into the stomach 1 week after the operation. ER stress signaling pathway molecules and apoptosis were studied in pressure-overloaded hearts 9 weeks after AAC.

Telmisartan significantly reduced LVH and interstitial fibrosis and improved left ventricular function compared with AAC alone. Cardiac markers of ER stress such as GRP78, C/EBP homologous protein, caspase-12 and phospho c-Jun NH2-terminal kinase were significantly increased in rats with AAC, and telmisartan significantly blunted these changes. Rats that received both telmisartan and AAC had less apoptosis due to ER stress.

Increased ER stress might be responsible for enhanced cardiomyocyte apoptosis after aortic coarctation. Telmisartan may reduce ER stress and thereby attenuate both apoptosis and cardiac hypertrophy.