[Functional decoupling of left ventricular beta-adrenoceptor in a canine model of obesity-hypertension].
OBJECTIVE
To assess cardiac beta-adrenoceptors (beta-AR) in an obesity-hypertension model.


METHODS
Six male beagle dogs (aged 35 +/- 5 months) receiving during 30 weeks a high-fat diet with 60% uncooked beef fat were compared to 6 normal beagle dogs. With right auricular and left ventricular samples we analysed cardiac beta-AR density through binding study using [125I]-cyanopindolol. beta 1 and beta 2 densities were obtained by competition with CGP 20712A. Affinity state of beta-AR was assessed by competition with isoproterenol. Noradrenaline plasma level was assayed by HPLC. Left ventricular mass (LV mass) was measured by echocardiography. Results are expressed as mean +/- SE. All comparisons were performed using a variance analysis (*: p < 0.05).


RESULTS
Systolic blood pressure was significantly higher in obesses (245 +/- 8 vs 197 +/- 10 mmHg in controls). Diastolic blood pressure did not differed between both groups (93 +/- 3 vs 84 +/- 3 mmHg in controls). Noradrenaline plasma levels were similar in both groups (276 +/- 30 vs 235 +/- 50 pg/mL in controls). Obesses were characterized by higher LV mass (80 +/- 24 vs 67 +/- 15 g in controls*). Right auricular and left ventricular beta-AR densities were not different in obesses (57 +/- 6 and 67 +/- 4 fmoles/mg protein) and in controls (68 +/- 7 and 63 +/- 9 fmoles/mg protein). The beta 1-AR proportion was the same in obesses and controls in right auricule (63 +/- 4 vs 64 +/- 3% in controls) and left ventricule (59 +/- 3 vs 60 +/- 4% in controls). The proportion of beta-AR receptors in a high affinity state was similar in right auricular samples (69 +/- 4 vs 67 +/- 3%) in controls) but was significantly different in left ventricule (28 +/- 6 vs 74 +/- 6%) in controls).


CONCLUSIONS
Left ventricular beta-adrenoceptors came under a specific desensibilisation independent of plasma noradrenaline levels. This functional decoupling of beta-adrenoceptors may account for the progressive systolic dysfunction of hypertensive cardiomyopathy.
Cabrol
P
P
Laboratoire de pharmacologie médicale et clinique, INSERM U317, Toulouse.
Galinier
M
M
Fourcade
J
J
Verwaerde
P
P
Massabuau
P
P
Tran
M A
MA
Montastruc
J L
JL
Bounhoure
J P
JP
Fauvel
J M
JM
Sénard
J M
JM
D000818:Animals; D004285:Dogs; D006352:Heart Ventricles / Q000378:metabolism*; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013599:Systole; D016277:Ventricular Function, Left
D011943:Receptors, Adrenergic, beta