Lymphocyte beta adrenoceptor upregulation and improved cardiac response to adrenergic stimulation following converting enzyme inhibition in congestive heart failure.
To determine the effect of ACE inhibitor therapy on lymphocyte beta-adrenoceptor function and density, as well as the in vivo myocardial response to beta-agonist stimulation, we studied 12 patients with chronic severe heart failure before and after 16 weeks' treatment with quinapril. Lymphocyte beta-adrenoceptor function (intracellular cAMP production in response to isoprenaline) was studied as a surrogate tissue for myocardium, and increased significantly after quinapril at concentrations of isoprenaline between 10(-3) and 50 mmol.l-1. Lymphocyte beta-adrenoceptor density (six patients) measured by [125I] iodocyanopindolol binding, increased from 242 +/- 72 (mean +/- SEM) to 884 +/- 17 receptors/cell (P < 0.05). Changes in functional myocardial beta-adrenoceptor status were determined by measuring changes in haemodynamic responses to exercise and to incremental dobutamine infusion. Following quinapril there were significant improvements in cardiac index, stroke volume and cardiac power output during sub-maximal exercise testing and dobutamine infusion; stroke work index in response to dobutamine (but not exercise) improved significantly. ACE inhibitors cause lymphocyte beta-adrenoceptor upregulation in heart failure, which is associated with an improved cardiac pumping capacity in response to beta-agonist stimulation.
Department of Cardiovascular Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, U.K.
J N
JN
Townend
S J
SJ
Virk
F X
FX
Qiang
N
N
Lawson
R J
RJ
Bain
M K
MK
Davies
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D002908:Chronic Disease; D004280:Dobutamine / Q000494:pharmacology; D015444:Exercise / Q000502:physiology; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology* / Q000627:therapeutic use; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D000077583:Quinapril; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D044005:Tetrahydroisoquinolines; D015854:Up-Regulation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D011943:Receptors, Adrenergic, beta; D044005:Tetrahydroisoquinolines; D004280:Dobutamine; D000077583:Quinapril