Cabrol P, Galinier M, Fourcade J, Verwaerde P, Massabuau P, Tran M A, Montastruc J L, Bounhoure J P, Fauvel J M, Sénard J M
Laboratoire de pharmacologie médicale et clinique, INSERM U317, Toulouse.
Arch Mal Coeur Vaiss. 1998 Aug;91(8):1021-4.
To assess cardiac beta-adrenoceptors (beta-AR) in an obesity-hypertension model.
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).
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).
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.
评估肥胖 - 高血压模型中的心脏β - 肾上腺素能受体（β - AR）。
将6只雄性比格犬（年龄35±5个月）在30周内给予含60%生牛肉脂肪的高脂饮食，并与6只正常比格犬进行比较。通过使用[125I] - 氰吲哚洛尔的结合研究，分析右心耳和左心室样本中的心脏β - AR密度。通过与CGP 20712A竞争获得β1和β2密度。通过与异丙肾上腺素竞争评估β - AR的亲和力状态。通过高效液相色谱法测定去甲肾上腺素血浆水平。通过超声心动图测量左心室质量（LV质量）。结果以平均值±标准误表示。所有比较均采用方差分析（*：p < 0.05）。
肥胖组的收缩压显著更高（245±8 mmHg，对照组为197±10 mmHg）。两组之间的舒张压无差异（93±3 mmHg，对照组为84±3 mmHg）。两组的去甲肾上腺素血浆水平相似（276±30 pg/mL，对照组为235±50 pg/mL）。肥胖组的特征是左心室质量更高（80±24 g，对照组为67±15 g*）。肥胖组和对照组的右心耳和左心室β - AR密度无差异（分别为57±6和67±4 fmol/mg蛋白）和（68±7和63±9 fmol/mg蛋白）。右心耳中β1 - AR比例在肥胖组和对照组中相同（63±4%，对照组为64±3%），左心室中也相同（59±3%，对照组为60±4%）。高亲和力状态下β - AR受体的比例在右心耳样本中相似（69±4%，对照组为67±3%），但在左心室中显著不同（28±6%，对照组为74±6%）。
左心室β - 肾上腺素能受体发生了特定的脱敏，与血浆去甲肾上腺素水平无关。β - 肾上腺素能受体的这种功能解偶联可能是高血压性心肌病进行性收缩功能障碍的原因。
