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Crosstalk between NO and cAMP signaling in basilar arteries from young and old mice
Author(s) -
Pfitzer Gabriele,
Lubomirov Lubomir T.,
Welter Johannes,
Weckmueller Kathrin,
Todorovic Nikola,
Papadopoulos Symeon
Publication year - 2013
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.27.1_supplement.901.14
Subject(s) - myograph , electrical impedance myography , medicine , endocrinology , basal (medicine) , basilar artery , crosstalk , chemistry , contraction (grammar) , anatomy , cardiology , vasodilation , physics , optics , insulin
The aim of this work was to elucidate whether aging affects crosstalk between NO and cAMP signaling in mouse basilar arteries. Isometric force was recorded by wire myography. In arteries from young mice inhibition of NOS with 100 μM L‐NAME increased basal tone by 9 % of F max (F max = max. contraction elicited by 1 μM U46619 + L‐NAME) and increased the pEC 50 value of U46619 from 6.5 to 7.1 (n = 6). Inhibition of nNOS by 1 μM L‐NPA increased all parameters by a similar extend (n = 3). Pretreatment with L‐NAME completely reduced immunoreactivity against pMYPT1‐S695, the PKG site. In arteries from aged animals, L‐NAME increased basal tone by 23 % of F max (n = 4), but L‐NPA only by 11 %. In the absence of NOS inhibitors, pEC 50 for U46619 was 7.0, comparable to that with L‐NAME or L‐NPA in young animals. Here, L‐NAME or L‐NPA increased pEC 50 for U46619 only by 0.3 log‐units. In both age groups, urocortin, which acts through cAMP, completely relaxed L‐NAME induced basal tone and submaximally preconstricted (0.3 μM U46619 + L‐NAME) vessels. Activation of Epac by 8‐pCPT‐O’‐Me‐cAMP (8‐pCPT) relaxed tone induced by NOS inhibition by ~40 % in both age groups. L‐NAME dramatically reduced relaxation of preconstricted arteries by 8‐pCPT in aged but not in young vessels. In conclusion, our results suggest that regulation of basal tone in basilar arteries is nNOS‐dependent in young mice and involves both n‐ and eNOS in old mice. We also provide evidence that NOS‐activity is required for dilation by the cAMP effector, Epac in aged arteries. Funding: DFG