[肥胖-高血压犬模型中左心室β-肾上腺素能受体的功能解偶联]

[Functional decoupling of left ventricular beta-adrenoceptor in a canine model of obesity-hypertension].

作者信息

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

机构信息

Laboratoire de pharmacologie médicale et clinique, INSERM U317, Toulouse.

出版信息

Arch Mal Coeur Vaiss. 1998 Aug;91(8):1021-4.

PMID:9749157

Abstract

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).

CONCLUSION

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.

摘要

目的

评估肥胖 - 高血压模型中的心脏β - 肾上腺素能受体（β - AR）。

方法

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）。

结果

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%）。