Beneficial effect of myocardial angiogenesis on cardiac remodeling processby amlodipine and MCI-154

The present study examined the effect of long-term treatment with amlodipin e and MCI-154 (a Ca2+ sensitizer) on progressive cardiac dysfunction and mi crovasculature in the dilated cardiomyopathic (DCM) hamster heart. After tr eatment of DCM hamsters (Bio 53.58) with amlodipine or MCI-154 for 15 wk fr om the age of 5 wk, amlodipine and MCI-154 were found to cause an increase in left ventricular percent fractional shortening and decreases in left ven tricular diastolic dimension and isovolumic relaxation time in echocardiogr ams (P < 0.01). A hemodynamic study showed that the diastolic time constant decreased in the amlodipine-treatment group (P < 0.05). In a morphometric study employing a double-staining method that discriminated arteriolar and venular capillaries, amlodipine and MCI-154 caused increases in total capil lary density (P < 0.05) and the proportion of venular capillaries (P < 0.05 ). Moreover, Northern blot analysis showed that the expression of mRNA for vascular endothelial growth factor was significantly increased by amlodipin e and MCI-154. They preserve coronary microvasculature in the DCM hamster a nd might induce angiogenesis of small vessels, thereby contributing to pres ervation of cardiac systolic and diastolic function.