Enalapril prevents cardiac fibrosis and arrhythmias in hypertensive rats.
To evaluate the effects of hypertension on cardiac hypertrophy, on myocardial structure, and on ventricular arrhythmias, 27 3-month-old spontaneously hypertensive rats were treated with enalapril (10 mg/kg) daily for 11 months and compared with 26 untreated control rats. Systolic arterial pressure was significantly decreased in treated rats, and at the end of the experiment, it was 199 +/- 3 mm Hg (treated) versus 237 +/- 3 mm Hg (controls) (p less than 0.001). At this time, spontaneous arrhythmias and induced arrhythmias either by programmed electrical stimulation (train of stimuli +1 or 2 extrastimuli) or by trains of eight stimuli at decreasing coupling intervals were observed in isolated heart preparations. Comparing enalapril-treated and control rats, spontaneous arrhythmias (9 of 27 versus 20 of 26, respectively; p less than 0.01), programmed stimulation-induced arrhythmias (3 of 26 versus 12 of 23, respectively; p less than 0.01), and trains of stimuli-induced arrhythmias (4 of 26 versus 14 of 19, respectively, p less than 0.001) were less frequent in the enalapril group. Left ventricular weight was decreased in treated rats by 18% (p less than 0.001). Enalapril administration diminished the fraction of myocardium occupied by foci of replacement fibrosis normally occurring in control rats by 59% (p less than 0.001). Finally, a significant correlation was found between left ventricular weight, the extent of myocardial fibrosis, and the occurrence of ventricular fibrillation. It was concluded that chronic treatment with enalapril, which resulted in attenuation of systemic arterial pressure by limiting cardiac hypertrophy and myocardial fibrosis, decreases the propensity of the heart of hypertensive rats to arrhythmogenesis.
Pahor
M
M
Divisione di Gerontologia, Università Cattolica del S. Cuore, Rome, Italy.
Bernabei
R
R
Sgadari
A
A
Gambassi
G
G
Lo Giudice
P
P
Pacifici
L
L
Ramacci
M T
MT
Lagrasta
C
C
Olivetti
G
G
Carbonin
P
P
D000704:Analysis of Variance; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004562:Electrocardiography; D004656:Enalapril / Q000494:pharmacology*; D004719:Endomyocardial Fibrosis / Q000473:pathology / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles; D006973:Hypertension / Q000150:complications; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D014693:Ventricular Fibrillation / Q000188:drug therapy
D004656:Enalapril