Effect of captopril on isoproterenol-induced cardiac hypertrophy and polyamine contents.
It is well known that isoproterenol (ISO) a nonselective beta adrenoceptor agonist induces cardiac hypertrophy. It can be assumed that, in addition to its direct cardiac effect, ISO has a cardiac trophic effect via stimulation of the renin angiotensin system. Synthesis of polyamines is facilitated in cardiac hypertrophy and polyamine levels are rapidly elevated prior to an increase in heart weight. In the present study, we investigated whether captopril (30 mg/kg body weight, daily) could attenuate cardiac hypertrophy and elevation of cardiac polyamine levels in rats, which effects were elicited by a chronic (1- or 2-weeks) and repeated administration of a small dose (0.5 mg/kg body weight) of ISO. Cardiac hypertrophy was assessed by an increase in the wet weight and RNA content of the heart. Polyamines were analyzed by HPLC. Captopril alone did not affect either heart weight/body weight ratio or cardiac contents of polyamines and nucleic acids at the end of the second week. In isoproterenol-treated rats, the above parameters, except for putrescine content on day 14, were significantly increased on both day 7 and day 14. Captopril slightly attenuated ISO-induced cardiac hypertrophy and significantly prevented the ISO-evoked increase in the contents of RNA, spermidine, and spermine at the end of the second week. These results suggest that the ISO-evoked increase in cardiac polyamines was mediated, at least in part, by the renin angiotensin system, which was stimulated by ISO.
Shimizu
M
M
Third Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Sasaki
H
H
Sanjo
J
J
Ogawa
K
K
Mizokami
T
T
Yagi
T
T
Kato
H
H
Hamaya
K
K
Namiki
A
A
Isogai
Y
Y
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D004247:DNA / Q000032:analysis; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011073:Polyamines / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects
D011073:Polyamines; D004247:DNA; D002216:Captopril; D007545:Isoproterenol