Premium
Induction of NOS and PDE5 isozymes in resistance arteries under chronic high and low flow
Author(s) -
Lee Hyon Jae,
Zhang Haiying,
Fisher Steven
Publication year - 2008
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.22.1_supplement.744.10
Subject(s) - ligation , signal transduction , blot , effector , medicine , gene isoform , phosphorylation , endocrinology , isozyme , mesenteric arteries , chemistry , microbiology and biotechnology , biology , gene , artery , biochemistry , enzyme
Myosin phosphatase (MP), the primary effector of smooth muscle relaxation, is a key target of signaling pathways that regulate vascular tone. Using the mesenteric artery ligation high flow/low flow model (HF/LF), we previously showed changes in MP isoform expression associated with increased sensitivity of VSM to NO/cGMP signaling. We hypothesized that altered expression of genes proximal in this pathway also influence NO/cGMP signaling under sustained HF/LF. Methods: Every other second order mesenteric artery (MA2) was ligated to induce LF in upstream MA1s and HF in adjacent MA1s. Rat MA1s were harvested 1‐28 days after ligation and assayed for gene expression by real time PCR. Results: Fold change vs. Control, Day4 Changes in NOS and PDE5 expression were confirmed at the protein level by Western blotting. Conclusion: This and the functional studies presented in the accompanying abstract suggest that induction of PDE5 de‐sensitizes vascular smooth muscle to NO signaling under sustained HF/LF conditions. These results provide a novel mechanism for the dynamic changes in NO signaling in HF and LF disease states. Supported by NIH R01 HL‐66171 and Case School of Medicine Crile Fellowship.