Lai E Y, Patzak A, Steege A, Mrowka R, Brown R, Spielmann N, Persson P B, Fredholm B B, Persson A E G
Department of Medical Cell Biology, Division of Physiology, University of Uppsala, Uppsala, Sweden.
Kidney Int. 2006 Aug;70(4):690-8. doi: 10.1038/sj.ki.5001650.
Adenosine (Ado) mediates vasoconstriction via A(1)-Ado receptors and vasodilation via A(2)-Ado receptors in the kidney. It interacts with angiotensin II (Ang II), which is important for renal hemodynamics and tubuloglomerular feedback (TGF). The aim was to investigate the function of Ado receptors in the Ado-Ang II interaction in mouse microperfused, afferent arterioles. Ado (10(-11)-10(-4) mol/l) caused a biphasic response: arteriolar diameters were reduced (-7%) at Ado 10(-11)-10(-9) mol/l and returned to control values at higher concentrations. Treatment with Ang II (10(-10) mol/l) transformed the response into a concentration-dependent constriction. N(6)-cyclopentyladenosine (A(1)-Ado receptor agonist) reduced diameters (12% at 10(-6) mol/l). Application of CGS21680 (10(-12)-10(-4) mol/l, A(2A) receptor agonist) increased the diameter by 13%. Pretreatment with ZM241385 (A(2A)-Ado receptor antagonist) alone or in combination with MRS1706 (A(2B)-Ado receptor antagonist) resulted in a pure constriction upon Ado, whereas 8-cyclopentyltheophylline (CPT) (A(1)-Ado receptor antagonist) inhibited the constrictor response. Afferent arterioles of mice lacking A(1)-Ado receptor did not show constriction upon Ado. Treatment with Ado (10(-8) mol/l) increased the response upon Ang II, which was blocked by CPT. Ado (10(-5) mol/l) did not influence the Ang II response, but an additional blockade of A(2)-Ado receptors enhanced it. The action of Ado on constrictor A(1)-Ado receptors and dilatory A(2)-Ado receptors modulates the interaction with Ang II. Both directions of Ado-Ang II interaction, which predominantly leads to an amplification of the contractile response, are important for the operation of the TGF.
腺苷（Ado）通过A（1）-Ado受体介导肾脏血管收缩，通过A（2）-Ado受体介导血管舒张。它与血管紧张素II（Ang II）相互作用，血管紧张素II对肾血流动力学和肾小管-肾小球反馈（TGF）很重要。目的是研究Ado受体在小鼠微灌注传入小动脉的Ado-Ang II相互作用中的功能。Ado（10^(-11)-10^(-4)mol/L）引起双相反应：Ado浓度为10^(-11)-10^(-9)mol/L时小动脉直径减小（-7%），浓度较高时恢复到对照值。用Ang II（10^(-10)mol/L）处理将反应转变为浓度依赖性收缩。N（6）-环戊基腺苷（A（1）-Ado受体激动剂）使直径减小（10^(-6)mol/L时为12%）。应用CGS21680（10^(-12)-10^(-4)mol/L，A（2A）受体激动剂）使直径增加13%。单独用ZM241385（A（2A）-Ado受体拮抗剂）或与MRS1706（A（2B）-Ado受体拮抗剂）联合预处理，Ado作用后导致单纯收缩，而8-环戊基茶碱（CPT）（A（1）-Ado受体拮抗剂）抑制收缩反应。缺乏A（1）-Ado受体的小鼠传入小动脉对Ado不显示收缩。用Ado（10^(-8)mol/L）处理可增强对Ang II的反应，这被CPT阻断。Ado（10^(-5)mol/L）不影响Ang II反应，但额外阻断A（2）-Ado受体可增强该反应。Ado对收缩性A（1）-Ado受体和舒张性A（2）-Ado受体的作用调节与Ang II的相互作用。Ado-Ang II相互作用的两个方向，其中主要导致收缩反应放大，对TGF的运作都很重要。
