Adenosine enhances long term the contractile response to angiotensin II in afferent arterioles.
Adenosine (Ado) enhances ANG II-induced constrictions of afferent arterioles (Af) by receptor-dependent and -independent pathways. Here, we test the hypothesis that transient Ado treatment has a sustained effect on 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 on ANG II in isolated, perfused Af. Cytosolic calcium transients on ANG II were not enhanced in Ado-treated vessels. Selective or global inhibition of A(1)- and A(2)-adenosine receptors did not inhibit the Ado effect. Nitrobenzylthioinosine (an Ado transport inhibitor) clearly reduced the Ado-mediated responses. Selective inhibition of p38 MAPK with SB-203580 also prevented the Ado effect. Inosine treatment did not influence arteriolar reactivity to ANG II. Contractile responses of Af on norepinephrine and endothelin-1 were not influenced by Ado. Phosphorylation of the p38 MAPK and of the regulatory unit of 20-kDa myosin light chain was enhanced after Ado treatment and ANG II in Af. However, phosphorylation of p38 MAPK induced by norepinephrine or endothelin-1 was reduced in vessels treated with Ado, whereas 20-kDa myosin light chain 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 tubuloglomerular feedback.
Patzak
Andreas
A
Institute of Vegetative Physiology, University Hospital Charité, Humboldt-University of Berlin, Berlin, Germany. andreas.patzak@charite.de
Lai
En Yin
EY
Fähling
Michael
M
Sendeski
Mauricio
M
Martinka
Peter
P
Persson
Pontus B
PB
Persson
A Erik G
AE
D000241:Adenosine / Q000008:administration & dosage*; D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D000804:Angiotensin II; D000241:Adenosine