Amelioration of cardiac remodeling in congestive heart failure by beta-adrenoceptor blockade is associated with depression in sympathetic activity.
This study investigated whether improvement in cardiac function and attenuation of cardiac remodeling by some beta-adrenoceptor (beta-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 beta-AR antagonists on cardiac remodeling and heart dysfunction in CHF may be due to the blockade of beta-ARs in the myocardium and a depression in the sympathetic activity.
Machackova
Jarmila
J
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
Sanganalmath
Santosh K
SK
Barta
Judit
J
Dhalla
Ken S
KS
Dhalla
Naranjan S
NS
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use* / Q000633:toxicity*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003864:Depression, Chemical; D004562:Electrocardiography / Q000187:drug effects; D004837:Epinephrine / Q000097:blood; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D001262:Atenolol; D011433:Propranolol; D009638:Norepinephrine; D004837:Epinephrine