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Amelioration of Cardiac Remodeling in Congestive Heart Failure by β-Adrenoceptor Blockade is Associated with Depression in Sympathetic Activity

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Abstract

This study investigated whether improvement in cardiac function and attenuation of cardiac remodeling by some β-adrenoceptor (β-AR) antagonists were associated with a depression in sympathetic activity in congestive heart failure (CHF) due to myocardial infarction (MI). Although cardiac dysfunction, hypertrophy and dilatation as well as increased plasma level of catecholamines are known to occur in CHF, the relationship between these parameters is poorly understood. Three weeks after occlusion of the coronary artery, rats were treated daily with 20 and 75 mg/kg of either atenolol or propranolol for 5 weeks. Sham-operated rats served as controls. Both atenolol and propranolol at 20 and 75 mg/kg doses attenuated the MI-induced cardiac hypertrophy, increases in left ventricular (LV) end-diastolic pressure, LV end-systolic volume and LV end-diastolic volume as well as depressions in LV systolic pressure, LV fractional shortening and cardiac output. PR interval was decreased and QT c interval was increased in CHF; these alterations were ameliorated by both atenolol and propranolol. The increased level of plasma epinephrine in CHF was also depressed by both low and high doses of atenolol and propranolol whereas the increased level of plasma norepinephrine was reduced by high but not low doses of these drugs. The results indicate that the beneficial effects of β-AR antagonists on cardiac remodeling and heart dysfunction in CHF may be due to the blockade of β-ARs in the myocardium and a depression in the sympathetic activity.

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Acknowledgments

Supported by a grant from the Canadian Institutes of Health Research. The infrastructural support was provided by the St. Boniface General Hospital Research Foundation. JM and JB were postdoctoral fellows supported by the IMPACT Program and the TACTICS Program of the CIHR, respectively.

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Authors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Avenue, Winnipeg, MB, R2H 2A6, Canada

    Jarmila Machackova, Santosh K. Sanganalmath, Judit Barta, Ken S. Dhalla & Naranjan S. Dhalla

  2. Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada

    Jarmila Machackova, Santosh K. Sanganalmath, Judit Barta, Ken S. Dhalla & Naranjan S. Dhalla

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  1. Jarmila Machackova
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  2. Santosh K. Sanganalmath
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  3. Judit Barta
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Correspondence to Naranjan S. Dhalla.

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Machackova, J., Sanganalmath, S.K., Barta, J. et al. Amelioration of Cardiac Remodeling in Congestive Heart Failure by β-Adrenoceptor Blockade is Associated with Depression in Sympathetic Activity. Cardiovasc Toxicol 10, 9–16 (2010). https://doi.org/10.1007/s12012-009-9058-y

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