Submitted on May 21, 2007
Accepted on September 20, 2007
Adenosine enhances long-term the contractile response to angiotensin II in afferent arterioles
Andreas Patzak1*, En Yin Lai2, Michael Fahling1, Mauricio Sendeski1, Peter Martinka1, Pontus B. Persson3, and A. Erik G. Persson2
1 Institute of Vegetative Physiology, Humboldt-University of Berlin, Charite-Universitatsmedizin Berlin, Berlin, Germany
2 Department of Medical Cell Biology, Uppsala University, Biomedical Center, Uppsala, Sweden
3 Institute of Vegetative Physiology, Humboldt-University of Berlin, Charite- Universitatsmedizin Berlin, Berlin, Germany
* To whom correspondence should be addressed. E-mail: andreas.patzak{at}charite.de.
Adenosine (Ado) enhances angiotensin II (Ang II) induced constrictions of afferent arterioles (Af) by receptor dependent and independent pathways. We test the hypothesis that transient Ado treatment has a sustained effect of Af contractility resulting in increased Ang II responses after longer absence of Ado. Treatment with Ado (cumulative from 10-11 to 10-4 mol/l) and consecutive washout for 10 or 30 min increased constrictions upon Ang II in isolated perfused Af. Cytosolic calcium transients upon Ang II were not enhanced in Ado treated vessels. Selective or global inhibition of A1- and A2-adenosine receptors did not inhibit the Ado effect. Nitrobenzylthioinosine (NBTI, Ado transport inhibitor), clearly reduced the Ado mediated responses. Selective inhibition of p38 mitogen activated protein kinase (MAPK) with SB203580 also prevented the Ado effect. Inosine treatment did not influence arteriolar reactivity to Ang II. Contractile responses of Af upon norepinephrine (NE) and endothelin 1 (ET-1) were not influenced by Ado. Phosphorylation of the p38 MAPK and of the regulatory unit of myosin light chain (MLC20) was enhanced after Ado treatment and Ang II in Af. However, phosphorylation of p38 MAPK induced by NE or ET 1 was reduced in vessels treated with Ado, while MLC20 was unchanged. The results suggest an intracellular, long lasting mechanism including p38 MAPK activation responsible for the increase of Ang II induced contractions by Ado. The effect is not calcium dependent and specific for Ang II. The prolonged enhancement of the Ang II sensitivity of Af may be important for the tubuloglomerular feedback.
