Effects of hydrochlorothiazide and captopril on the survival and heart weight of cardiomyopathic hamsters.
The current study investigated the effect of hydrochlorothiazide (HCTZ), and of captopril, on the survival and heart weight of cardiomyopathic hamsters (CMH). Groups of 51 CMH (about 200 days old) were orally treated with HCTZ (6 mg/kg), captopril (30 mg/kg), a combination of both drugs or vehicle alone (control group), for 217 days. Then survivors were sacrificed and the hearts weighed. The survival of the animals treated with HCTZ alone or in combination with captopril was similar, and was clearly increased when compared to controls (more than 70 days increase in median survival time). A more modest increase in survival occurred in animals treated with captopril alone. The efficacy of the diuretic therapy was consistent with fluid retention being the primary cause of death in CMH and demonstrated the usefulness of the model for the testing of new diuretics. HCTZ or captopril alone had no effect on the heart weight of survivors. However a reduction of cardiac hypertrophy (-18%) was seen when captopril and HCTZ were coadministered. This effect of the ACE inhibitor was considered to result from antagonism of the compensatory activation of the renin-angiotensin system occurring in response to diuretic therapy.
Hanton
G
G
Centre de Recherche Pfizer, Amboise, France.
Barnes
P
P
Shepperson
N B
NB
Walley
R
R
D000818:Animals; D002216:Captopril / Q000008:administration & dosage / Q000627:therapeutic use*; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006224:Cricetinae; D004359:Drug Therapy, Combination; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009206:Myocardium / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects
D006852:Hydrochlorothiazide; D002216:Captopril