Adenosine restores angiotensin II-induced contractions by receptor-independent enhancement of calcium sensitivity in renal arterioles
2006 (English)In: Circulation Research, ISSN 0009-7330, E-ISSN 1524-4571, Vol. 99, no 10, 1117-1124 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2006. Vol. 99, no 10, 1117-1124 p.
Adenosine, Afferent arterioles, Angiotensin II, Calcium sensitivity, Desensitization, Kidney, Myosin light chain
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-95567DOI: 10.1161/01.RES.0000249530.85542.d4ISI: 000242171900014PubMedID: 17038642OAI: oai:DiVA.org:uu-95567DiVA: diva2:169836