Adenosine A1 receptor‐dependent and independent pathways in modulating renal vascular responses to angiotensin II. (9th October 2014)

• Record Type: Journal Article
• Authors: Gao, X.; Peleli, M.; Zollbrecht, C.; Patzak, A.; Persson, A. E. G.; Carlström, M.
• Is Part Of: Acta physiologica. Volume 213:Number 1(2015:Jan.)
• Page Start: 268
• Page End: 276
• Publication Date: 2014-10-09
• Subjects: Physiology -- Periodicals; Physiology -- Research -- Periodicals; 612
• DOI: 10.1111/apha.12399
• Languages: English
• ISSNs: 1748-1708

Abstract

<abstract abstract-type="main" id="apha12399-abs-0001"> <title>Abstract</title> <sec id="apha12399-sec-0001" sec-type="section"> <title>Aim</title> <p>Renal afferent arterioles are the effector site for autoregulation of glomerular perfusion and filtration. There is synergistic interaction between angiotensin II (ANG II) and adenosine (Ado) in regulating arteriolar contraction; however, the mechanisms are not clear. In this context, this study investigated the contribution of A<sub>1</sub> receptor‐dependent and independent signalling mechanisms.</p> </sec> <sec id="apha12399-sec-0002" sec-type="section"> <title>Methods</title> <p>Isolated perfused afferent arterioles from transgenic mice (A<sub>1</sub><sup>+/+</sup> and A<sub>1</sub><sup>−/−</sup>) were used for vascular reactivity studies. Cultured vascular smooth muscle cells (VSMC) were used for phosphorylation studies of signalling proteins that induce arteriolar contraction.</p> </sec> <sec id="apha12399-sec-0003" sec-type="section"> <title>Results</title> <p>Maximal arteriolar contraction to ANG II was attenuated in A<sub>1</sub><sup>−/−</sup> (22%) compared with A<sub>1</sub><sup>+/+</sup> (40%). Simultaneous incubation with low‐dose ado (10<sup>−8</sup> mol L<sup>−1</sup>) enhanced ANG II‐induced contraction in A<sub>1</sub><sup>+/+</sup> (58%), but also in A<sub>1</sub><sup>−/−</sup> (42%). An ado transporter inhibitor (NBTI) abolished this synergistic effect in A<sub>1</sub><sup>−/−</sup>, but not in wild‐type mice. Incubation with Ado + ANG II increased p38 phosphorylation in aortic VSMC from both genotypes, but treatment with NBTI only blocked phosphorylation in A<sub>1</sub><sup>−/−</sup>. Combination of ANG II + Ado also increased MLC phosphorylation in A<sub>1</sub><sup>+/+</sup> but not significantly in A<sub>1</sub><sup>−/−</sup>, and NBTI had no effects. In agreement, Ado + ANG II‐induced phosphorylation of p38 and MLC in rat pre‐glomerular VSMC was not affected by NBTI. However, during pharmacological inhibition of the A<sub>1</sub> receptor simultaneous treatment with NBTI reduced phosphorylation of both p38 and MLC to control levels.</p> </sec> <sec id="apha12399-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Interaction between ANG II and Ado in VSMC normally involves A<sub>1</sub> receptor signalling, but this can be compensated by receptor independent actions that phosphorylate p38 MAPK and MLC.</p> </sec> </abstract>