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Pre‐exposing Skeletal Muscle Arterioles to Adenosine Alters the Role of PKA in Adenosine Mediated Arteriolar Dilation
Author(s) -
Maymon Nir,
Sarelius Ingrid H.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.817.3
We showed previously that skeletal muscle (SKM) arteriolar dilation to adenosine (Ado) is mediated by A 2A adenosine receptors via adenylate cyclase and K ATP channel activation (FASEB J. 2009 23:767.12). In the present study we further explored the signaling that mediates Ado induced vasodilation of mouse cremaster arterioles (<40 μm diameter). Previous data from our lab (J Physiol. 2004 Mar 1; 555(Pt 2):459) implicated endothelial cell (EC) Ca 2+ in mouse cremaster SKM contraction induced dilation. Using fluo‐4, we now show a significant increase in EC Ca 2+ in response to Ado. Furthermore, the cyclic nucleotide‐gated channel (CNGC) blocker L‐Cis‐Diltiazem abolished the increase in EC Ca 2+ and significantly attenuated arteriolar dilation to Ado. We also tested whether cAMP generated by A 2A receptor stimulation is acting on its downstream target PKA to mediate dilation. Interestingly, while PKA inhibition significantly blocked Ado dilation as expected, pre‐exposure to Ado abolished this inhibition, suggesting that Ado pre‐exposure alters signaling pathways that mediate dilation. Pre‐exposure to Ado did not alter the contribution of K ATP and CNG channels to Ado‐dependent dilation, indicating that the effect of ado pre‐exposure is specific to PKA signaling. Thus, our data indicate a novel vascular pre‐exposure effect of ado for which the physiological significance is not yet clear. (Supported by HL76414)