Hemin Enhances Cardiac Performance in Response to Pressure Overload (PO): Implications for Treatment of Heart Failure

Abstract

Myocardial hypertrophy induced by PO leads to heart failure. We reported previously that hemin reduces hypertrophy and enhances cardiac performance in response to PO in rat. Here, we investigated the mechanism by which hemin enhances cardiac function in response to PO. Animals were treated two days prior- and every three days postoperatively after banding of the ascending aorta for 10 weeks. Morphometric analysis revealed that hemin prevented PO-induced hypertrophy. Pressure-volume analysis revealed enhanced cardiac performance in banded and sham animals treated with hemin. To investigate the positive inotropic effect of hemin, single cell action potential duration, fractional shortening, and calcium transients were assessed. Sham animals treated with hemin displayed increased calcium transients under normal and β-adrenergic stimulation suggesting that the positive inotropic effect of hemin is mediated via alterations in calcium release. Because hemin stimulates CO production via induction of HO-1, we tested whether the anti-hypertrophic action of hemin is mediated via cGMP, by inhibiting its production with ODQ. Treatment with ODQ prevented the anti-hypertrophic effect of hemin but not the positive inotropic effect, suggesting that the anti-hypertrophic and inotropic effects of hemin are mediated by independent signaling mechnisms. Supported by grants from CIHR and HSFO to LG Melo and CA Ward.