Galinier M, Sénard J M, Valet P, Arias A, Daviaud D, Glock Y, Bounhoure J P, Montastruc J L
Service de Cardiologie et de Chirurgie Cardiovasculaire, Centre Hospitalier Universitaire Rangueil, Toulouse, France.
Fundam Clin Pharmacol. 1994;8(1):90-9. doi: 10.1111/j.1472-8206.1994.tb00784.x.
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.
在因主动脉狭窄导致左心室肥厚（LVH）的患者以及作为对照的无LVH但因二尖瓣狭窄或冠状动脉疾病接受心脏手术的患者中，研究了慢性压力超负荷引起的LVH对右心房（RA）和左心室（LV）心肌β-肾上腺素能受体（β-AR）密度及亚型、腺苷酸环化酶（AC）活性和ADP-百日咳毒素核糖基化蛋白的影响。两组患者的收缩功能或血浆儿茶酚胺水平均正常。在LVH组和对照组中，RA的β-AR密度相似（62±6对77±12 fmol·mg⁻¹蛋白质），LV的β-AR密度也相似（39±7对32±2 fmol·mg⁻¹蛋白质）。在LVH组中，LV的β1-AR百分比低于对照组（35±11对73±5%，P<0.05），但RA中的β1-AR百分比无差异（79±5对73±8%）。LVH组和对照组中，RA的基础AC活性相似（19±4对21±6 pmol·mg⁻¹蛋白质），LV的基础AC活性也相似（22±5对27±3 pmol·mg⁻¹蛋白质）。异丙肾上腺素诱导的RA中AC刺激在LVH组和对照组中相似（51±18对36±18%），但LVH组LV中的刺激低于对照组（7±6对45±6%，P<0.05）。在存在ICI-118,551（一种β2-肾上腺素能受体拮抗剂）的情况下，异丙肾上腺素未能诱导LVH组cAMP增加。ADP-百日咳毒素核糖基化蛋白的定量显示，LVH组LV心肌膜中底物浓度较低。这些数据表明，在压力超负荷引起的LVH中，存在β1-AR下调和β2-AR密度增加。这与跨膜信号转导改变有关，其特征是异丙肾上腺素刺激AC的能力降低以及Gi蛋白表达受损。
