Cardiac beta-adrenoceptors and adenylyl cyclase activity in human left ventricular hypertrophy due to pressure overload.
The effect of left ventricular hypertrophy (LVH) due to chronic pressure overload on right atrial (RA) and left ventricular (LV) myocardial beta-adrenergic receptor (beta-AR) density and subtypes, adenylyl cyclase (AC) activity and ADP-pertussis toxin ribosylated proteins was investigated in humans with LVH due to aortic stenosis and in patients without LVH undergoing heart surgery for mitral stenosis or coronary artery disease taken as controls. Both groups presented normal systolic function or plasma catecholamine levels. In LVH and controls, beta-AR density was similar in RA (62 +/- 6 vs 77 +/- 12 fmol.mg-1 protein) and LV (39 +/- 7 vs 32 +/- 2 fmol.mg-1 protein). In LVH, beta 1-AR percentage was < than in controls in LV (35 +/- 11 vs 73 +/- 5%, P < 0.05) but not in RA (79 +/- 5 vs 73 +/- 8%). Basal AC activity in RA (19 +/- 4 vs 21 +/- 6 pmol.mg-1 protein) and LV (22 +/- 5 vs 27 +/- 3 pmol.mg-1 protein) was similar in LVH and in controls. Isoprenaline-induced stimulation of AC in RA was similar in LVH and in controls (51 +/- 18 vs 36 +/- 18%) but < in LV of LVH (7 +/- 6 vs 45 +/- 6%, P < 0.05). In the presence of ICI-118,551 (a beta 2-adrenoceptor antagonist), isoprenaline failed to induce any increase in cAMP in LVH. The quantification of ADP-pertussis toxin ribosylated proteins indicated a lower concentration of substrates in LV myocardial membranes from LVH. These data indicate that in LVH due to pressure overload, there is a down-regulation of beta 1-AR and an increase in beta 2-AR density. This is associated with alterations of the transmembrane signalling marked by a decreased capacity of isoprenaline to stimulate AC and an impaired expression of Gi proteins.
Galinier
M
M
Service de Cardiologie et de Chirurgie Cardiovasculaire, Centre Hospitalier Universitaire Rangueil, Toulouse, France.
Sénard
J M
JM
Valet
P
P
Arias
A
A
Daviaud
D
D
Glock
Y
Y
Bounhoure
J P
JP
Montastruc
J L
JL
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000368:Aged; D001024:Aortic Valve Stenosis / Q000150:complications / Q000378:metabolism; D002395:Catecholamines / Q000097:blood; D003327:Coronary Disease / Q000378:metabolism; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008946:Mitral Valve Stenosis / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D017725:Ventricular Pressure
D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases