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Contribution of adenosine receptors in the control of arteriolar tone and adenosine-angiotensin II interaction
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrativ Fysiologi.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrativ Fysiologi.
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2006 (English)In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 70, no 4, 690-698 p.Article in journal (Refereed) Published
Abstract [en]

Adenosine (Ado) mediates vasoconstriction via A(1)-Ado receptors and vasodilation via A(2)-Ado receptors in the kidney. It interacts with angiotensin II (Ang II), which is important for renal hemodynamics and tubuloglomerular feedback (TGF). The aim was to investigate the function of Ado receptors in the Ado -Ang II interaction in mouse microperfused, afferent arterioles. Ado (10(-11)-10(-4) mol/l) caused a biphasic response: arteriolar diameters were reduced (-7%) at Ado 10(-11)-10(-9) mol/l and returned to control values at higher concentrations. Treatment with Ang II (10(-10) mol/l) transformed the response into a concentration-dependent constriction. N-6-cyclopentyladenosine (A(1)-Ado receptor agonist) reduced diameters (12% at 10(-6) mol/l). Application of CGS21680 (10(-12)-10(-4) mol/l, A(2A) receptor agonist) increased the diameter by 13%. Pretreatment with ZM241385 (A(2A)-Ado receptor antagonist) alone or in combination with MRS1706 (A(2B)-Ado receptor antagonist) resulted in a pure constriction upon Ado, whereas 8-cyclopentyltheophylline (CPT) (A(1)-Ado receptor antagonist) inhibited the constrictor response. Afferent arterioles of mice lacking A(1)-Ado receptor did not show constriction upon Ado. Treatment with Ado (10(-8) mol/l) increased the response upon Ang II, which was blocked by CPT. Ado (10(-5) mol/l) did not influence the Ang II response, but an additional blockade of A(2)-Ado receptors enhanced it. The action of Ado on constrictor A(1)-Ado receptors and dilatory A(2)-Ado receptors modulates the interaction with Ang II. Both directions of Ado-Ang II interaction, which predominantly leads to an amplification of the contractile response, are important for the operation of the TGF.

Place, publisher, year, edition, pages
2006. Vol. 70, no 4, 690-698 p.
Keyword [en]
adenosine, afferent arteriole, adenosine-angiotensin II interaction, mouse, adenosine type 1 receptor knockout mouse
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-95565DOI: 10.1038/sj.ki.5001650ISI: 000240015100019PubMedID: 16807541OAI: oai:DiVA.org:uu-95565DiVA: diva2:169834
Available from: 2007-03-07 Created: 2007-03-07 Last updated: 2011-06-21Bibliographically 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.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 237
Physiology, adenosine, angiotensin II, afferent arteriole, calcium, nitric oxide, microperfusion, tubuloglomerular feedback, Fysiologi
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
Available from: 2007-03-07 Created: 2007-03-07 Last updated: 2011-02-22Bibliographically approved

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