Enalapril prevents cardiac fibrosis and arrhythmias in hypertensive rats.

Abstract

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 ing/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<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.

Inhibition of Angiotensin-Converting Enzyme Reduces Susceptibility of Hypertrophied Rat Myocardium to Ventricular Fibrillation.

“…Furthermore, ischemic zone sizes (consisting of hypertrophied myocardium) were also similar among the VF hearts with AC. These observations indicate that regression of hypertrophied LV mass does not play a major role in attenuation of ventricular arrhythmias, which is contrary to the previous studies 8,15,16,19 that suggested that regression of hypertrophied ventricular mass is necessary for suppression of ventricular arrhythmias. It should be pointed out, however, that with our treatment protocol, ramipril significantly altered both the dimensions and the developmental phenotype of myocytes in hypertrophied myocardium even without regression of LV mass.…”

“…39 Such a reactive increase in collagen may explain why ramipril failed to reduce the LV weight. The increase in collagen quantity after the treatment with ACEI contrasts with the earlier studies 15,16 and is probably because of the different treatment duration. Indeed, Pahor et al showed that long-term treatment (11 months) with the ACEI enarapril significantly decreased both LV weight and fibrous tissue fraction.…”

“…8,[15][16][17]19 However, the relative contribution of myocyte and nonmyocyte components to arrhythmogenesis in hypertrophied myocardium has never been examined, and how regression of hypertrophy mediates attenuation of arrhythmias is still unclear.…”

Activation of angiotensinogen and angiotensin-converting enzyme gene expression in the left ventricle of senescent rats.

“…ACEI have been reported to reduce LV hypertrophy in response to cardiac overload.48'49 ACEI given to old normotensive rats decreased arterial stiffening and LV mass.50 Such a treatment prevents cardiac fibrosis and arrhythmias in old hypertensive rats. 51 In conclusion, this work shows an activation of ANG and ACE gene expression in the aged LV that is likely to have a mechanical origin and is associated with a parallel increase in cardiac ANF. With aging, the activity of the plasma RAS is decreased, suggesting that the elderly must be more sensitive to ACEI therapy.…”

The Role of the Renin-Angiotensin System in Cardiovascular Disease.

“…In addition, after enalapril treatment, an upregulation of AOGEN and renin gene expression has been reported (166) suggesting a negative feedback of ANG II on the pathway. Furthermore, other models of left ventricular hypertrophy, like SHR or isoproterenol-infused rats, respond very sensitive to CEI by a reduction in left ventricular weight accompanied by a regression in myocardial fibrosis (171)(172)(173)(174). These changes were not correlated with blood pressure reduction or plasma ANG II levels but with a fall in cardiac ANG II concentrations (173,174).…”