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Upregulation of the adenylyl cyclase/cAMP signaling pathway in aorta from interleukin‐6 (IL‐6) knockout mice.
Author(s) -
Todd Joseph,
Teixeira Cleber Evandro,
Webb R. Clinton
Publication year - 2006
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.20.5.a1117-a
Subject(s) - adenylyl cyclase , endocrinology , medicine , forskolin , phenylephrine , chemistry , sodium nitroprusside , stimulation , nitric oxide , blood pressure
OBJECTIVE Cytokines induce genes that synthesize peptides in the cytokine family and several mediators, all of which can affect vascular function. We aimed to provide an insight into the vascular effects of IL‐6 by investigating the responses to drugs that signal through the cGMP and cAMP pathways. METHODS Aortic rings from wild‐type (WT) and IL‐6 KO mice were mounted in 5‐ml myographs and isometric force was recorded. cAMP was measured using EIA kits. RESULTS Contractions evoked by phenylephrine (0.001–10 μM) or U46619 (0.0001–0.3 μM) were not different between rings from WT and IL‐6 KO mice. Sensitivity to clonidine was not different (WT: 6.41 ± 0.03; IL‐6 KO: 6.27 ± 0.03), but maximal responses were reduced by 45% in IL‐6 KO rings. Endothelium‐dependent or independent relaxations to acetylcholine (0.001–10 μM) or sodium nitroprusside (0.0001‐1 μM), respectively, were not altered in IL‐6 KO preparations. However, relaxations to the adenylyl cyclase activator forskolin (FK, 0.001–10 μM) were shifted to the left by 3‐fold in IL‐6 KO rings (pEC 50 values of 6.85 ± 0.07 in WT and 7.37 ± 0.05 in IL‐6 KO). Basal levels of cAMP (pmol/mg protein) were higher in IL‐6 KO rings (13.3 ± 1.1 vs 5.6 ± 0.7). FK‐induced cAMP increases were enhanced in IL‐6 KO rings at 0.1 μM (33.9 ± 3.3 vs 15.7 ± 2.0) and 1 μM (49.0 ± 4.2 vs 37.4 ± 3.9). CONCLUSION IL‐6 specifically downregulates the adenylyl cyclase/cAMP pathway in the mouse aorta. Support: HL74167, AHA.