Patil Jaspal, Stucki Silvan, Nussberger Juerg, Schaffner Thomas, Gygax Susanne, Bohlender Juergen, Imboden Hans
Institute of Cell Biology, University of Bern, Bern, Switzerland.
Regul Pept. 2011 Feb 25;167(1):31-41. doi: 10.1016/j.regpep.2010.11.011. Epub 2010 Dec 9.
Although the physiological and pharmacological evidences suggest a role for angiotensin II (Ang II) with the mammalian heart, the source and precise location of Ang II are unknown. To visualize and quantitate Ang II in atria, ventricular walls and interventricular septum of the rat and human heart and to explore the feasibility of local Ang II production and function, we investigated by different methods the expression of proteins involved in the generation and function of Ang II. We found mRNA of angiotensinogen (Ang-N), of angiotensin converting enzyme, of the angiotensin type receptors AT(1A) and AT₂ (AT(1B) not detected) as well as of cathepsin D in any part of the hearts. No renin mRNA was traceable. Ang-N mRNA was visualized by in situ hybridization in atrial ganglial neurons. Ang II and dopamine-β-hydroxylase (DβH) were either colocalized inside the same neuronal cell or the neurons were specialized for Ang II or DβH. Within these neurons, the vesicular acetylcholine transporter (VAChT) was neither colocalized with Ang II nor DβH, but VAChT-staining was found with synapses en passant encircle these neuronal cells. The fibers containing Ang II exhibited with blood vessels and with cardiomyocytes supposedly angiotensinergic synapses en passant. In rat heart, right atrial median Ang II concentration appeared higher than septal and ventricular Ang II. The distinct colocalization of neuronal Ang II with DβH in the heart may indicate that Ang II participates together with norepinephrine in the regulation of cardiac functions: produced as a cardiac neurotransmitter Ang II may have inotropic, chronotropic or dromotropic effects in atria and ventricles and contributes to blood pressure regulation.
尽管生理学和药理学证据表明血管紧张素II（Ang II）在哺乳动物心脏中发挥作用，但其来源和确切位置尚不清楚。为了可视化并定量大鼠和人类心脏的心房、心室壁和室间隔中的Ang II，并探索局部Ang II产生和功能的可行性，我们采用不同方法研究了参与Ang II生成和功能的蛋白质表达。我们在心脏的任何部位都发现了血管紧张素原（Ang-N）、血管紧张素转换酶、血管紧张素1型受体AT(1A)和AT₂（未检测到AT(1B)）以及组织蛋白酶D的mRNA。未检测到肾素mRNA。通过原位杂交在心房神经节神经元中观察到Ang-N mRNA。Ang II和多巴胺-β-羟化酶（DβH）要么共定位于同一神经元细胞内，要么这些神经元专门表达Ang II或DβH。在这些神经元中，囊泡乙酰胆碱转运体（VAChT）既不与Ang II也不与DβH共定位，但在环绕这些神经元细胞的过路突触处发现了VAChT染色。含有Ang II的纤维与血管以及推测为血管紧张素能过路突触的心肌细胞一起出现。在大鼠心脏中，右心房中部的Ang II浓度似乎高于室间隔和心室的Ang II。心脏中神经元Ang II与DβH的明显共定位可能表明Ang II与去甲肾上腺素一起参与心脏功能的调节：作为一种心脏神经递质产生的Ang II可能在心房和心室中具有变力、变时或变传导作用，并有助于血压调节。
