Published online before print October 12, 2006, doi: 10.1161/01.RES.0000249530.85542.d4
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Submitted on May 29, 2006
Revised on September 28, 2006
Accepted on September 29, 2006
Adenosine Restores Angiotensin II-Induced Contractions by Receptor-Independent Enhancement of Calcium Sensitivity in Renal Arterioles
En Yin Lai ;
From the Department of Medical Cell Biology (E.Y.L., A.E.G.P.), Division of Physiology, University of Uppsala, Sweden; Johannes-Müller-Institute of Physiology (P.M., M.F., R.M., A.S., A.G., M.S., P.B.P., A.P.), University Hospital Charité, Humboldt-University of Berlin; and Institute of Biology (A.S.), Free University of Berlin, Germany.
* To whom correspondence should be addressed. E-mail: andreas.patzak{at}charite.de.
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.
Key words: adenosine • angiotensin II • desensitization • calcium sensitivity • myosin light chain • afferent arterioles • kidney
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