FUNCTIONAL DECOUPLING OF LEFT-VENTRICULAR BETA-ADRENOCEPTOR IN A CANINE MODEL OF OBESITY-HYPERTENSION

Objective : To assess cardiac beta-adrenoceptors (beta-AR) in an obesi ty-hypertension model. Methods: Six male beagle dogs (aged 35 +/- 5 mo nths) receiving during 30 weeks a high-fat diet with 60 % uncooked bee f fat were compared to 6 normal beagle dogs. With right auricular and left ventricular samples we analysed cardiac beta-AR density through b inding study using [I-125]-cyanopindolol. beta 1 and beta 2 densities were obtained by competition with CGP 20712A. Affinity state of beta-A R was assessed by competition with isoproterenol. Noradrenaline plasma level was assayed by HPLC. Left ventricular mass (LV mass) was measur ed by echocardiography. Results are expressed as mean +/- SE. All comp arisons were performed using a variance analysis ( : p < 0,05). Resul ts : Systolic blood pressure was significantly higher in obeses (245 /- 8 vs 197 +/- 10 mmHg in controls). Diastolic blood pressure did not differed between both groups (93 +/- 3vs 84 +/- 3 mmHg in controls). Noradrenaline plasma levels were similar in both groups (276 +/- 30 vs 235 +/- 50 pg/mL in controls). Obeses were characterized by higher LV mass (80 +/- 24 vs 67 +/- 15 g in controls). Right auricular and lef t ventricular beta-AR densities were not different in obeses (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 obeses and controls in right auricule (63 +/- 4 vs 64 +/- 3 % in controls) an d left ventricule (59 +/- 3 vs 60 +/- 4 % in controls). The proportion of beta-AR receptors in a high affinity state was similar in right au ricular samples (69 +/- 4 vs 67 +/- 3 %) in controls) but was signific antly different in left ventricule (28 +/- 6 vs 74 +/- 6 %) in control s). Conclusion: Left ventricular beta-adrenoceptors came under a speci fic desensibilisation independent of plasma noradrenaline levels. This functional decoupling of beta-adrenoceptors may account for the progr essive systolic dysfunction of hypertensive cardiomyopathy.