Fior D R, Yang S N, Ganten U, Ganten D, Fuxe K
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Brain Res. 1995 May 8;679(1):168-77. doi: 10.1016/0006-8993(95)00220-k.
An interaction between angiotensin II (Ang II) receptors and alpha 2-adrenoceptors was evaluated in the nucleus tractus solitarii (NTS) of the normotensive Wistar-Kyoto rat (WKY) and of the spontaneously hypertensive rat (SHR) using quantitative receptor autoradiography and cardiovascular analysis. In the WKY rat, Ang II promoted a dose-dependent increase in the IC50 value of l-noradrenaline when competing for ([3H]p-aminoclonidine ([3H]PAC) binding sites, which reached a maximum of 400% with 10 nM of Ang II and was associated with a small decrease in the B0 value (20%). In the SHR Ang II (0.1 nM) had an opposite effect leading to a decrease in the IC50 value of about 57%, and no change was observed in the B0 value. Saturation analysis also showed that Ang II (0.1 nM) increased the KD value of [3H]PAC in the WKY strain but in contrast decreased the KD value of [3H]PAC in the SHR. The Bmax value was not significantly changed neither in the WKY rat nor in the SHR. The cardiovascular analysis showed that a threshold dose of Ang II (0.05 pmol) counteracted the vasodepressor effect produced by l-noradrenaline coinjected in the NTS of the WKY rat. No effect was observed in heart rate. In the SHR no counteraction of the l-noradrenaline-induced vasodepressor effect was found, and in contrast a slight increase of the vasodepressor effect associated with a significant increase in the bradycardiac response was observed. The results give evidence for an antagonistic Ang II/alpha 2 receptor interaction in the cardiovascular part of the NTS of the WKY rat as previously observed in the Sprague-Dawley rat. However, this interaction is altered in the SHR, so that in this strain the Ang II/alpha 2 receptor interaction enhances alpha 2 affinity and possibly alpha 2 receptor function. This opposite effect observed in the SHR may represent one compensatory mechanism to counteract the development of high blood pressure in the SHR.
利用定量受体放射自显影术和心血管分析，在正常血压的Wistar-Kyoto大鼠（WKY）和自发性高血压大鼠（SHR）的孤束核（NTS）中评估了血管紧张素II（Ang II）受体与α2-肾上腺素能受体之间的相互作用。在WKY大鼠中，当与[3H]对氨基可乐定（[3H]PAC）结合位点竞争时，Ang II促使去甲肾上腺素的IC50值呈剂量依赖性增加，10 nM的Ang II使其增加至最大值400%，并伴有B0值小幅下降（20%）。在SHR中，0.1 nM的Ang II产生相反作用，导致IC50值下降约57%，且B0值未观察到变化。饱和分析还显示，0.1 nM的Ang II增加了WKY品系中[3H]PAC的KD值，但相反，降低了SHR中[3H]PAC的KD值。WKY大鼠和SHR中的Bmax值均未发生显著变化。心血管分析表明，阈剂量的Ang II（0.05 pmol）可抵消在WKY大鼠NTS中共同注射的去甲肾上腺素产生的血管减压作用。心率未观察到影响。在SHR中，未发现对去甲肾上腺素诱导的血管减压作用有拮抗作用，相反，观察到血管减压作用略有增加，并伴有明显的心动过缓反应增加。结果证明，如先前在Sprague-Dawley大鼠中观察到的那样，在WKY大鼠NTS的心血管部分存在Ang II/α2受体拮抗相互作用。然而，这种相互作用在SHR中发生了改变，因此在该品系中，Ang II/α2受体相互作用增强了α2亲和力并可能增强了α2受体功能。在SHR中观察到的这种相反作用可能代表了一种抵消SHR中高血压发展的代偿机制。
