Verapamil Accelerates the Transition to Heart Failure in Obese, Hypertensive, Female SHHF/Mcc-facp Rats

We sought to characterize the effects of the non-selective Ca channel antagonist, verapamil, and the vascular-selective Ca channel antagonist, felodipine, on obese, hypertensive, heart failure-prone, female SHHF/Mcc-fa rats. Rats were treated for ≤2 months with verapamil (57 mg/kg/day) or felodipine (24 mg/kg/day). Blood pressures were determined at monthly intervals by the tail-cuff method. Heart weights and myosin isoforms were measured at the end of treatment. Direct cardiac effects of verapamil and felodipine were examined in electrically field stimulated, fura-2/AM-loaded cardiomyocytes. Both Ca channel antagonists reduced systolic blood pressures. Verapamil, but not felodipine, increased heart weights and decreased expression of the myosin V1 isoform. In older animals, 75% of those treated with verapamil developed end-stage congestive heart failure. Age-matched control and felodipine-treated rats remained healthy. In isolated cardiomyocytes, 10 M verapamil significantly reduced Ca transient amplitudes but 10 M felodipine did not. Both Ca channel antagonists reduced blood pressures in obese, hypertensive, female SHHF rats. Verapamil, but not felodipine, produced heart failure in a large number of these animals. Differences between the in vivo effects of the two Ca channel antagonists may be related to the differing effects on sarcolemmal Ca influx.