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 antagonist, felodipine, on obese, hypertensive, heart failure-prone, female SHHF/Mcc-fa(cp) rats. Rats were treated for < or = 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 Ca2+ 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(-9) M verapamil significantly reduced Ca2+ transient amplitudes but 10(-9) M felodipine did not. Both Ca2+ 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 Ca2+ channel antagonists may be related to the differing effects on sarcolemmal Ca2+ influx.
Park
S
S
Department of Food Science and Technology, The Ohio State University, Columbus 43210-1218, USA.
McCune
S A
SA
Radin
M J
MJ
Hoepf
T M
TM
Hensley
J
J
Hohl
C M
CM
Altschuld
R A
RA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000009:adverse effects* / Q000494:pharmacology; D015736:Felodipine / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009218:Myosins / Q000096:biosynthesis; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D014700:Verapamil / Q000009:adverse effects* / Q000494:pharmacology
D002121:Calcium Channel Blockers; D014700:Verapamil; D009218:Myosins; D015736:Felodipine