Authors: Hansen, P. B.; Friis, U. G.¹; Uhrenholt, T. R.¹; Briggs, J.²; Schnermann, J.²

Source: Acta Physiologica, Volume 191, Number 2, October 2007 , pp. 89-97(9)

Publisher: Wiley-Blackwell

Abstract:

Aims: 

Adenosine causes vasoconstriction of afferent arterioles of the mouse kidney through activation of adenosine A₁ receptors and Gi-mediated stimulation of phospholipase C. In the present study, we further explored the signalling pathways by which adenosine causes arteriolar vasoconstriction. Methods and results: 

Adenosine (10⁻⁷ m) significantly increased the intracellular calcium concentration in mouse isolated afferent arterioles measured by fura-2 fluorescence. Pre-treatment with thapsigargin (2 μm) blocked the vasoconstrictor action of adenosine (10⁻⁷ m) indicating that release of calcium from the sarcoplasmic reticulum (SR), stimulated presumably by IP₃, is involved in the adenosine contraction mechanism of the afferent arteriole. In agreement with this notion is the observation that 2 aminoethoxydiphenyl borate (100 μm) blocked the adenosine-induced constriction whereas the protein kinase C inhibitor calphostin C had no effect. The calcium-activated chloride channel inhibitor IAA-94 (30 μm) inhibited the adenosine-mediated constriction. Patch clamp experiments showed that adenosine treatment induced a depolarizing current in preglomerular smooth muscle cells which was abolished by IAA-94. Furthermore, the vasoconstriction caused by adenosine was significantly inhibited by 5 μmnifedipine (control 8.3 ± 0.2 μm, ado 3.6 ± 0.6 μm, ado + nifedipine 6.8 ± 0.2 μm) suggesting involvement of voltage-dependent calcium channels. Conclusion: 

We conclude that adenosine mediates vasoconstriction of afferent arterioles through an increase in intracellular calcium concentration resulting from release of calcium from the SR followed by activation of Ca²⁺-activated chloride channels leading to depolarization and influx of calcium through voltage-dependent calcium channels.

Keywords: adenosine; muscle smooth; renal circulation

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1748-1716.2007.01724.x

Affiliations: 1:  Department of Physiology and Pharmacology, University of Southern Denmark, Odense, Denmark 2:  National Institute of Diabetes, and Digestive and Kidney Diseases, NIH, Bethesda, MD, USA

Publication date: 2007-10-01

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