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Adenosine restores angiotensin II-induced contractions by receptor-independent enhancement of calcium sensitivity in renal arterioles
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
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2006 (English)In: Circulation Research, ISSN 0009-7330, E-ISSN 1524-4571, Vol. 99, no 10, 1117-1124 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
Adenosine, Afferent arterioles, Angiotensin II, Calcium sensitivity, Desensitization, Kidney, Myosin light chain
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-95567DOI: 10.1161/01.RES.0000249530.85542.d4ISI: 000242171900014PubMedID: 17038642OAI: oai:DiVA.org:uu-95567DiVA: diva2:169836
Available from: 2007-03-07 Created: 2007-03-07 Last updated: 2011-02-22Bibliographically approved
In thesis
1. Interaction between Adenosine and Angiotensin II in Renal Afferent Arterioles of Mice
Open this publication in new window or tab >>Interaction between Adenosine and Angiotensin II in Renal Afferent Arterioles of Mice
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Renal arterioles represent the most important effecter site in the control of renal perfusion and filtration. Adenosine (Ado), angiotensin II (Ang II) and nitric oxide (NO) interact in modulating arteriolar tone. The present work investigates the mechanism of this interaction. We tested the hypothesis that AT1 receptor (AT1AR) mediated NO release in isolated perfused afferent arterioles. Further, special attention was given to mechanisms of Ado-Ang II -interactions.

We found (I) that Ang II specifically induces NO release via AT1AR in arterioles. The effect is important in view of high renin and Ang II concentrations in these vessels. (II) Ado modulates the Ang II response by acting on vasoconstrictor A1AR and vasodilator A2AR. Vice versa, Ang II critically enhances the constriction to Ado, which supports the assumption of its modulating action in the tubuloglomerular feedback (TGF). (III) The synergistic effect of Ang II and Ado on arteriolar contraction is concurrent with an increase in the cytosolic calcium. Further, (IV) Ado increases the calcium sensitivity of the contractile machinery in arteriolar smooth muscle cells most probably by enhancement of the phosphorylation of the myosin light chain regulatory unit. RhoA kinase, protein kinase C and p38 MAP are involved in the Ado effect, which is not receptor mediated and depends on the Ado uptake into vascular cells. Remarkably, the enhancing action of Ado is most likely limited to Ang II; since Ado does not influence endothelin-1 and norepinephrine induced contractions.

These novel results extend our knowledge about the synergistic action of Ang II and Ado in the control of renal filtration. Ado, the key factor in mediation of the TGF, develops a significant vasoconstrictor action only in the presence of Ang II. On the other hand, the Ang II induced vasoconstriction is modulated by Ado via receptor and non-receptor mediated intracellular signaling pathways.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 48 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 237
Keyword
Physiology, adenosine, angiotensin II, afferent arteriole, calcium, nitric oxide, microperfusion, tubuloglomerular feedback, Fysiologi
Identifiers
urn:nbn:se:uu:diva-7702 (URN)978-91-554-6822-4 (ISBN)
Public defence
2007-04-20, B7:113a, BMC, Husarg. 3, Box 571, 751 23 UPPSALA, Uppsala, 09:15
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Available from: 2007-03-07 Created: 2007-03-07 Last updated: 2011-02-22Bibliographically approved

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