Patzak Andreas, Lai En Yin, Fähling Michael, Sendeski Mauricio, Martinka Peter, Persson Pontus B, Persson A Erik G
Institute of Vegetative Physiology, University Hospital Charité, Humboldt-University of Berlin, Berlin, Germany.
Am J Physiol Regul Integr Comp Physiol. 2007 Dec;293(6):R2232-42. doi: 10.1152/ajpregu.00357.2007. Epub 2007 Sep 26.
Adenosine (Ado) enhances ANG II-induced constrictions of afferent arterioles (Af) by receptor-dependent and -independent pathways. Here, we test the hypothesis that transient Ado treatment has a sustained effect on Af contractility, resulting in increased ANG II responses after longer absence of Ado. Treatment with Ado (cumulative from 10(-11) to 10(-4) mol/l) and consecutive washout for 10 or 30 min increased constrictions on ANG II in isolated, perfused Af. Cytosolic calcium transients on ANG II were not enhanced in Ado-treated vessels. Selective or global inhibition of A(1)- and A(2)-adenosine receptors did not inhibit the Ado effect. Nitrobenzylthioinosine (an Ado transport inhibitor) clearly reduced the Ado-mediated responses. Selective inhibition of p38 MAPK with SB-203580 also prevented the Ado effect. Inosine treatment did not influence arteriolar reactivity to ANG II. Contractile responses of Af on norepinephrine and endothelin-1 were not influenced by Ado. Phosphorylation of the p38 MAPK and of the regulatory unit of 20-kDa myosin light chain was enhanced after Ado treatment and ANG II in Af. However, phosphorylation of p38 MAPK induced by norepinephrine or endothelin-1 was reduced in vessels treated with Ado, whereas 20-kDa myosin light chain was unchanged. The results suggest an intracellular, long-lasting mechanism including p38 MAPK activation responsible for the increase of ANG II-induced contractions by Ado. The effect is not calcium dependent and specific for ANG II. The prolonged enhancement of the ANG II sensitivity of Af may be important for tubuloglomerular feedback.
腺苷（Ado）通过受体依赖性和非依赖性途径增强血管紧张素II（ANG II）诱导的入球小动脉（Af）收缩。在此，我们检验以下假设：短暂的Ado处理对Af收缩性具有持续影响，导致在更长时间未使用Ado后ANG II反应增强。用Ado（浓度从10^(-11)至10^(-4) mol/l累积）处理并连续洗脱10或30分钟可增加分离的灌注Af对ANG II的收缩。在Ado处理的血管中，ANG II引起的细胞溶质钙瞬变未增强。选择性或整体抑制A(1)和A(2) - 腺苷受体均未抑制Ado的作用。硝基苄硫基肌苷（一种Ado转运抑制剂）明显降低了Ado介导的反应。用SB - 203580选择性抑制p38丝裂原活化蛋白激酶（MAPK）也可阻止Ado的作用。肌苷处理不影响小动脉对ANG II的反应性。Af对去甲肾上腺素和内皮素 - 1的收缩反应不受Ado影响。Ado处理和ANG II作用后，Af中p38 MAPK和20 kDa肌球蛋白轻链调节单位的磷酸化增强。然而，在Ado处理的血管中，去甲肾上腺素或内皮素 - 1诱导的p38 MAPK磷酸化降低，而20 kDa肌球蛋白轻链不变。结果提示一种细胞内的持久机制，包括p38 MAPK活化，负责Ado增加ANG II诱导的收缩。该作用不依赖钙且对ANG II具有特异性。Af对ANG II敏感性的长期增强可能对球管反馈很重要。
