Lai En Yin, Martinka Peter, Fähling Michael, Mrowka Ralf, Steege Andreas, Gericke Adrian, Sendeski Mauricio, Persson P B, Persson A Erik G, Patzak Andreas
Department of Medical Cell Biology, Division of Physiology, University of Uppsala, Sweden.
Circ Res. 2006 Nov 10;99(10):1117-24. doi: 10.1161/01.RES.0000249530.85542.d4. Epub 2006 Oct 12.
Adenosine is coupled to energy metabolism and regulates tissue blood flow by modulating vascular resistance. In this study, we investigated isolated, perfused afferent arterioles of mice, which were subjected to desensitization during repeated applications of angiotensin II. Exogenously applied adenosine restores angiotensin II-induced contractions by increasing calcium sensitivity of the arterioles, along with augmented phosphorylation of the regulatory unit of the myosin light chain. Adenosine restores angiotensin II-induced contractions via intracellular action, because inhibition of adenosine receptors do not prevent restoration, but inhibition of NBTI sensitive adenosine transporters does. Restoration was prevented by inhibition of Rho-kinase, protein kinase C, and the p38 mitogen-activated protein kinase, which modulate myosin light chain phosphorylation and thus calcium sensitivity in the smooth muscle. Furthermore, adenosine application increased the intracellular ATP concentration in LuciHEK cells. The results of the study suggest that restoration of the angiotensin II-induced contraction by adenosine is attributable to the increase of the calcium sensitivity by phosphorylation of the myosin light chain. This can be an important component of vascular control during ischemic and hypoxic conditions. Additionally, this mechanism may contribute to the mediation of the tubuloglomerular feedback by adenosine in the juxtaglomerular apparatus of the kidney.
腺苷与能量代谢相关联，并通过调节血管阻力来调控组织血流。在本研究中，我们研究了分离灌注的小鼠传入小动脉，这些小动脉在重复应用血管紧张素II的过程中会发生脱敏。外源性应用的腺苷通过增加小动脉的钙敏感性以及增强肌球蛋白轻链调节单位的磷酸化，来恢复血管紧张素II诱导的收缩。腺苷通过细胞内作用恢复血管紧张素II诱导的收缩，因为抑制腺苷受体并不能阻止恢复，但抑制NBTI敏感的腺苷转运体则可以。抑制Rho激酶、蛋白激酶C和p38丝裂原活化蛋白激酶可阻止恢复，这些激酶可调节肌球蛋白轻链磷酸化，从而调节平滑肌中的钙敏感性。此外，应用腺苷可增加LuciHEK细胞内的ATP浓度。该研究结果表明，腺苷恢复血管紧张素II诱导的收缩归因于肌球蛋白轻链磷酸化导致的钙敏感性增加。这可能是缺血和缺氧条件下血管控制的一个重要组成部分。此外，这种机制可能有助于腺苷在肾脏近球小体中介导肾小管-肾小球反馈。
