Premium
Adenosine A 1 receptor‐dependent and independent pathways in modulating renal vascular responses to angiotensin II
Author(s) -
Gao X.,
Peleli M.,
Zollbrecht C.,
Patzak A.,
Persson A. E. G.,
Carlström M.
Publication year - 2015
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12399
Subject(s) - phosphorylation , angiotensin ii , medicine , endocrinology , receptor , adenosine , vascular smooth muscle , chemistry , contraction (grammar) , microbiology and biotechnology , biology , smooth muscle
Aim 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 1 receptor‐dependent and independent signalling mechanisms. Methods Isolated perfused afferent arterioles from transgenic mice (A 1 +/+ and A 1 −/− ) were used for vascular reactivity studies. Cultured vascular smooth muscle cells ( VSMC ) were used for phosphorylation studies of signalling proteins that induce arteriolar contraction. Results Maximal arteriolar contraction to ANG II was attenuated in A 1 −/− (22%) compared with A 1 +/+ (40%). Simultaneous incubation with low‐dose ado (10 −8 mol L −1 ) enhanced ANG II ‐induced contraction in A 1 +/+ (58%), but also in A 1 −/− (42%). An ado transporter inhibitor ( NBTI ) abolished this synergistic effect in A 1 −/− , 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 1 −/− . Combination of ANG II + Ado also increased MLC phosphorylation in A 1 +/+ but not significantly in A 1 −/− , 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 1 receptor simultaneous treatment with NBTI reduced phosphorylation of both p38 and MLC to control levels. Conclusion Interaction between ANG II and Ado in VSMC normally involves A 1 receptor signalling, but this can be compensated by receptor independent actions that phosphorylate p38 MAPK and MLC .