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[Echocardiographic analysis of the effect of different Na+/H+ exchanger inhibitors on left ventricular structure and
Eduardo M Escudero1, Ana L Tufare, Irene L Ennis
1Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Argentina. cicme@atlas.med.unip.edu.ar
Insights
Two Na+/H+ exchange inhibitors, HOE 642 and BIIB 723, reduced left ventricular mass in hypertensive rats. Despite increased peak systolic stress, cardiac function remained stable, suggesting potential inotropic effects.
Area of Science:
- Cardiology
- Pharmacology
- Hypertension Research
Background:
- Left ventricular (LV) hypertrophy is a common complication of hypertension.
- Na+/H+ exchange (NHE) inhibitors have shown potential in treating cardiovascular diseases.
- Understanding the effects of specific NHE inhibitors on cardiac structure and function is crucial.
Purpose of the Study:
- To evaluate the impact of HOE 642 and BIIB 723 on left ventricular mass and systolic function in spontaneously hypertensive rats.
- To assess the effects of these inhibitors on blood pressure and peak systolic stress.
Main Methods:
- Echocardiography was used to assess cardiac parameters in spontaneously hypertensive rats.
- Rats were treated with HOE 642 or BIIB 723 (30 mg/kg/day) for 30 days.
- Control rats received no treatment.
Main Results:
- Both HOE 642 and BIIB 723 significantly reduced left ventricular mass.
- A slight decrease in blood pressure was observed with HOE 642, but not BIIB 723.
- Both drugs increased peak systolic stress without altering LV endocardial fractional shortening.
Conclusions:
- Long-term treatment with HOE 642 and BIIB 723 effectively reduces left ventricular mass in hypertensive rats.
- These NHE inhibitors maintain cardiac function despite increased systolic stress, potentially indicating enhanced inotropism.
- Further research is warranted to explore the therapeutic implications of these findings.
Abstract:
The aim of this study was to analyze by echocardiogram, the action of two Na+/H+ exchange, inhibitors, HOE 642 (HOE) and BIIB 723 (BIIB) on left ventricular (LV) mass and LV systolic function. We studied 16 spontaneously hypertensive rats (SHR), 8 treated with HOE 30 mg/kg/day, 8 with 30 mg/kg/day of BIIB during 30 days and 4 SHR as controls during those 30 days. Results are expressed as mean values +/- SEM. The systolic blood pressure and the echocardiograpic parameters examined did not evidence changes during that period in the controls rats. Even though HOE determined a slight decrease in blood pressure (HOE C: 184 +/- 1.75 mm Hg; HOE 30d: 176.20 +/- 2.60 mm Hg - p < 0.01) which was not detected with BIIB, both drugs provoked an increase of peak systolic stress (HOE C: 166 +/- 29 kdynes/cm2; HOE 30d: 204 +/- 34 kdynes/cm2, p < 0.04; BIIB C: 164 +/- 25.90 kdynes/ cm2; BIIB 30d: 234 +/- 29.30 kdynes/cm2, p < 0.02). HOE and BIIB reduced LV mass after 30 days of administration (HOE C: 612.50 +/- 50 mg; 30d: 452 +/- 37 mg, p < 0.01. BIIB C: 544 +/- 16mg; 30d: 374 +/- 25 mg, p < 0.01). LV endocardial shortening was similar independently of the NHE inhibitors used (HOE C: 62.30 +/- 2.75%; 30d: 65.50 +/- 2.40%, ns. BIIB C: 63.20 +/- 2,39%; 30d 67,20 +/- 1.62%, ns). These data demonstrate that long-treatment with HOE or BIIB produced similar LV mass regression without changes in endocardial fractional shortening in spite of the increase of peak systolic stress. This finding could represent an increased inotropism previously depressed by the development of hypertrophy.
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