Nozawa T, Igawa A, Yoshida N, Maeda M, Inoue M, Yamamura Y, Asanoi H, Inoue H
2nd Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
Circulation. 1998 Jun 16;97(23):2359-67. doi: 10.1161/01.cir.97.23.2359.
Heart failure is associated with activation of the sympathetic nervous system and downregulation of beta-receptors. However, the coupling between cardiac sympathetic neuronal function and the beta-receptor during the development of hypertensive heart failure is not clear.
We determined cardiac neuronal function and beta-receptors with a dual-tracer method of [131I]metaiodobenzylguanidine (MIBG) and 125I-cyanopindolol (ICYP) in Dahl salt-sensitive (DS) and salt-resistant (DR) rats. The rats were fed an 8% NaCl diet after the age of 6 weeks. Blood pressure was raised to >200 mm Hg at 12 weeks in DS rats and remained elevated until 18 weeks, but only slightly in DR rats. Left ventricular (LV) function of DS rats was preserved at 12 weeks but deteriorated at 18 weeks. Despite a 56% reduction of cardiac norepinephrine (NE) content at 12 weeks in DS rats, neither MIBG nor ICYP uptake in DS rats was different from that of DR rats. At 18 weeks, both MIBG and ICYP uptakes decreased, by 52% and 39%, respectively, in association with 71% reduction of cardiac NE, in DS rats. MIBG uptake of the LV was homogeneous at 6 weeks but was lower in the LV endocardial regions at 18 weeks in DS rats.
The present results indicate that cardiac sympathetic neuronal function is relatively preserved at the compensated, hypertrophic stage of DS rats but deteriorates in association with beta-receptor downregulation at the failing stage. The cardiac neuronal dysfunction occurs heterogeneously. A combination of scintigraphic portrayal of beta-receptors with MIBG should provide valuable information regarding sympathetic nerve signaling in living hearts.
心力衰竭与交感神经系统激活及β受体下调有关。然而，高血压性心力衰竭发展过程中心脏交感神经元功能与β受体之间的耦合尚不清楚。
我们采用[131I]间碘苄胍（MIBG）和125I-氰基吲哚洛尔（ICYP）双示踪法，在 Dahl 盐敏感（DS）和盐抵抗（DR）大鼠中测定心脏神经元功能和β受体。6周龄后，给大鼠喂食8%氯化钠饮食。12周时，DS大鼠血压升至>200 mmHg，并持续升高至18周，而DR大鼠血压仅略有升高。DS大鼠左心室（LV）功能在12周时保持正常，但在18周时恶化。尽管DS大鼠在12周时心脏去甲肾上腺素（NE）含量降低了56%，但其MIBG和ICYP摄取与DR大鼠并无差异。18周时，DS大鼠的MIBG和ICYP摄取均下降，分别下降了52%和39%，同时心脏NE减少了71%。DS大鼠6周时LV的MIBG摄取均匀，但18周时LV心内膜区域的摄取较低。
目前的结果表明，在DS大鼠的代偿性肥厚阶段，心脏交感神经元功能相对保留，但在衰竭阶段随着β受体下调而恶化。心脏神经元功能障碍呈异质性发生。将β受体的闪烁显像与MIBG相结合，应为活体心脏交感神经信号传导提供有价值的信息。
