title: Adenosine restores angiotensin II-induced contractions by receptor-independent enhancement of calcium sensitivity in renal arterioles.
abstract: 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.
authors.affiliation: Department of Medical Cell Biology, Division of Physiology, University of Uppsala, Sweden.
authors.forename: En Yin
authors.initials: EY
authors.lastname: Lai
authors.forename: Peter
authors.initials: P
authors.lastname: Martinka
authors.forename: Michael
authors.initials: M
authors.lastname: Fähling
authors.forename: Ralf
authors.initials: R
authors.lastname: Mrowka
authors.forename: Andreas
authors.initials: A
authors.lastname: Steege
authors.forename: Adrian
authors.initials: A
authors.lastname: Gericke
authors.forename: Mauricio
authors.initials: M
authors.lastname: Sendeski
authors.forename: P B
authors.initials: PB
authors.lastname: Persson
authors.forename: A Erik G
authors.initials: AE
authors.lastname: Persson
authors.forename: Andreas
authors.initials: A
authors.lastname: Patzak
mesh_terms: D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D007551:Isotonic Contraction / Q000187:drug effects; D007668:Kidney / Q000098:blood supply*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D054460:rho-Associated Kinases
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D018994:Myosin Light Chains; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D000804:Angiotensin II; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D000241:Adenosine; D002118:Calcium