VERAPAMIL ACCELERATES THE TRANSITION TO HEART-FAILURE IN OBESE, HYPERTENSIVE, FEMALE SHHF MCC-FA(CP) RATS/

We sought to characterize the effects of the nonselective Ca2+ channel antagonist, verapamil, and the vascular-selective Ca2+ channel antago nist, felodipine, on obese, hypertensive, heart failure-prone, female SHHF/Mcc-fa(cp) rats. Rats were treated for less than or equal to 2 mo nths with verapamil (57 mg/kg/day) or felodipine <less than or equal ( 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 felo dipine were examined in electrically field stimulated, fura-2/AM-loade d cardiomyocytes. Both Ca2+ channel antagonists reduced systolic blood pressures. Verapamil, but not felodipine, increased heart weights and decreased expression of the myosin V-1 isoform. In older animals, 75% of those treated with verapamil developed end-stage congestive heart failure. Age-matched control and felodipine-treated rats remained heal thy. In isolated cardiomyocytes, 10(-9) M verapamil significantly redu ced Ca2+ transient amplitudes but 10(-9) M felodipine did not. Both Ca -2+ channel antagonists reduced blood pressures in obese, hypertensive , female SHHF rats. Verapamil, but not felodipine, produced heart fail ure in a large number of these animals. Differences between the in viv o effects of the two Ca2+ channel antagonists may be related to the di ffering effects on sarcolemmal Ca2+ influx.