Cardiac hypertrophy has reached epidemic proportions worldwide and with no solid evidence of an independent benefit beyond blood pressure control newer therapeutic strategies have to be designed. It has been known since long that hypertension leads to hypertrophy, which disrupts the normal homeostatic mechanisms. We undertook this problem with a view to understand the mechanisms involved in the hypertrophic (two-kidney one-clip; 2K1C) heart subjected to ischemia-reperfusion or hypoxia-reoxygenation challenge.

          The study was divided into two parts, the first dealing with the calcium regulatory mechanisms and the second with the Nitric Oxide to assess the performance of hypertrophic hearts during ischemia-reperfusion injury. Evaluation was done for both functional and cellular responses by performing contraction studies and peroxynitrite estimations in whole heart preparations, whereas intracellular calcium, nitrite/nitrate ratio and total ROS estimations were done in myocytes. Assessment was done using various nitric oxide modulators such as L-NAME (NOS inhibitor), SNP (NO donor), L-arginine (NO supplement) and uric acid (ONOO- scavenger). The results suggest that Nitric oxide synthase inhibition by L-NAME offers a strong strategy that gives protection to the hypertrophic heart during ischemia-reperfusion injury, in terms of functional changes and providing protection from cytotoxic effects of peroxynitrite. At cellular level it lowered intracellular calcium transients, attenuated reactive oxygen species generation and maintained a stable mitochondrial membrane potential.

         With Ca2+ and NO taking center-stage during ischemia-reperfusion injury, this is the first time that an elaborate cross talk between these two key events has being reported in the hypertrophic rat heart