Renal hypertensive hypertrophy in the rat: a substrate for arrhythmogenicity

Abstract

We investigated the ability of ouabain to produce lethal arrhythmias in rats with myocardial hypertrophy resulting from chronic renal hypertension. A gradual pressure overload was produced in female Wistar rats by left renal artery stenosis (two kidney, one clip, Goldblatt hypertension). Hypertension (systolic blood pressure greater than 150 mm Hg) developed within three weeks after clipping of the left renal artery and blood pressure continued to increase for the next five weeks. At ten weeks after the onset of hypertension animals were anesthetized with sodium pentobarbital (40 mg/kg) and artificially ventilated with room air while ECG was continually monitored and recorded. Continuous infusion of ouabain was maintained (0.7 mg/kg/min) through the inferior vena cava. Body weight and heart rate of control animals (C) was not significantly different from hypertensive (H) values, while systolic blood pressure in animals hypertensive for ten weeks was considerably greater (187 +/- 8.4 mm Hg) than their age-matched normotensive counterparts (123 +/- 6.0 mm Hg). Heart weight in hypertensive animals was elevated by 69% +/- 2.5 by time of study. Serological evaluation of both groups of animals revealed no significant differences in electrolytes and blood gases while significant differences were noted in glucose, BUN and creatinine. The average time to the first premature ventricular contraction was significantly shorter in H animals (3.5 +/- 0.2 min) when compared to C rats (6.0 +/- 0.2 min). The average time to ventricular tachycardia, ventricular fibrillation and death were also significantly shorter in H rats when compared to C animals (7.5 +/- 0.6 vs. 13.5 +/- 0.3; 13.5 +/- 0.5 vs. 21.0 +/- 0.5; 15.6 +/- 0.4 vs. 24.0 +/- 0.6 min). Thus, the hypertensive hypertrophied myocardium displays an increased propensity for lethal cardiac arrhythmias due to ouabain.

Selective inhibitors of cardiac ADPR cyclase as novel anti-arrhythmic compounds

“…In vivo, as mentioned above, Gul et al (2009) demonstrated a pronounced increase in cardiac ADPR cyclase activity and cADPR levels in a rat 2K1C model that is characterised by increased angiotensin-II levels, hypertension and cardiac hypertrophy. Interestingly, 2K1C rats display an increased propensity towards ouabain-induced ventricular arrhythmia (Capasso et al 1986) which was shown to be improved in our study here by administration of inhibitors of cardiac ADPR cyclase.…”

Ouabain arrhythmogenicity in hypertrophied right and left ventricle of the rat

“…The results of the present study are in general agreement with the data of Capasso and coworkers (2). In both works it has been shown that arrhythmogenicity of ouabain is increased in the presence of myocardial hypertrophy.…”

“…It has already been proved that the arrhythmogenicity of digitalis is increased in rats with left ventricular hypertrophy due to experimental renal hypertension (2). However, in explanation of this finding, the possible electrolyte imbalance secondary to reduced renal excretory function, has to be considered as one of the possible causes of the lower electrical stability of the myocardial cell membrane, i.e., of the increased arrhythmogenicity of ouabain.…”

“…Experiments were performed on three groups of male albino rats: (1) rats with right ventricular hypertrophy secondary to experimental chronic hypoxic pulmonary hypertension (CH rats), (2) *) This work was supported by a grant from the Serbian Research Foundation 412 spontaneously hypertensive rats with left ventricular hypertrophy (SH rats) and (3) a control group of normal Wistar rats. Altogether, 40 rats were used throughout the experiment.…”

“…The greater arrhythmogenicity of ouabain in hypertrophied myocardium has been demonstrated experimentally in rats with hypertrophy of the left ventricle resulting from chronic renal hypertension (2). Left ventricles hypertrophied as a consequence of other experimental procedures have not been tested for sensitivity to the arrhythmogenic effect of ouabain.…”