Myocardial beta-adrenoceptors in pacing-induced heart failure: regulation by enalapril?
In heart failure, both the sympathetic nervous system and the renin angiotensin system play important pathophysiological roles, and the two systems may interact with each other, e.g., angiotensin II facilitating noradrenaline release. An abnormality in beta-adrenoceptor density (i.e., a decrease) occurs in clinical and pacing-induced heart failure. This observation together with the therapeutic effectiveness of converting-enzyme inhibitors in the management of patients with heart failure led to the current investigation. The aim was to explore the impact of chronic enalapril treatment on the status of myocardial beta-adrenoceptors in dogs paced (250 beats.min-1) to end-stage heart failure. Placebo or enalapril treatment (5 mg b.i.d.) commenced 1 week after the onset of ventricular pacing and continued until end-stage heart failure was reached. Myocardial beta-adrenoceptor density and affinity were assessed by radioligand binding with [125I]iodocyanopindolol. Left ventricular angiotensin II formation and noradrenaline concentration were measured. In addition, plasma renin activity and plasma noradrenaline levels were determined. The results showed that there was a significant increase in beta-adrenoceptor density following enalapril treatment compared with placebo in the heart-failure group. Enalapril did not change the beta-adrenoceptor density in the control animals. However, in both heart failure and control animals, enalapril caused an unexpected increase in Kd. Furthermore, in heart failure, enalapril caused a significant increase in myocardial angiotensin II formation. We conclude that enalapril prevents or reverses the myocardial beta-adrenoceptor abnormality seen in heart failure and promotes angiotensin II formation.
Department of Medicine, University of Toronto, St. Michael's Hospital, ON, Canada.
C
C
Forster
G O
GO
Naik
G
G
Larosa
D000804:Angiotensin II / Q000096:biosynthesis; D000818:Animals; D002303:Cardiac Output, Low / Q000503:physiopathology*; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004656:Enalapril / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D010869:Pindolol / Q000031:analogs & derivatives; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012083:Renin / Q000097:blood
D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D000804:Angiotensin II; D004656:Enalapril; D020120:Iodocyanopindolol; D010869:Pindolol; D012083:Renin; D009638:Norepinephrine