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Preservation of nitric oxide-induced relaxation of porcine coronary artery: roles of the dimers of soluble guanylyl cyclase, phosphodiesterase type 5, and cGMP-dependent protein kinase

  • Signaling and cell physiology
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Abstract

Soluble guanylyl cyclase (sGC), phosphodiesterase type 5 (PDE5), and guanosine 3′,5′-cyclic monophosphate (cGMP)-dependent protein kinase (PKG) are all dimeric. The present study was to determine the role of their dimeric status in nitric oxide-induced vasodilatation. In isolated porcine coronary arteries, after 20 h incubation with serum-free medium, serum-containing medium, or phosphate-buffered saline solution, the protein levels of the dimers of sGC, PDE5, and PKG were diminished while the monomer levels remained unchanged, associated with reduced cGMP elevation in response to DETA NONOate and decreased PDE5 activity; the activity of PKG was not significantly altered. DETA NONOate caused a greater relaxation in arteries incubated for 20 vs. 2 h. The relaxant response was largely abolished by 1H-[1, 2, 4]oxadiazolo[4,3-a]quinoxalin-1-one, an sGC inhibitor. Zaprinast, a PDE5 inhibitor, had no effect on relaxation caused by DETA NONOate of arteries incubated for 20 h but augmented the response incubated for 2 h. A greater relaxation to 8-bromo-guanosine 3′5′-cyclic monophosphate occurred in arteries incubated for 20 than for 2 h. The protein level of the dimers but not monomers of PDE5 was reduced by dithiothreitol and unaffected by hydrogen peroxide, accompanied with decreased PDE5 activity and reduced response to DETA NONOate. These results demonstrate that the dimeric but not monomeric status of sGC and PDE5 of coronary arteries are closely related to their activities. The preserved vasodilator response after 20 h incubation may result in part from a synchronous reduction of the dimer levels of sGC and PDE5 as well as an augmented response to cGMP.

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Acknowledgments

This work was supported in part by the National Natural Science Foundation of China grants 81270341.

Conflict of Interest

The authors state no conflict of interest.

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Authors and Affiliations

  1. Department of Physiology and Pathophysiology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing, 100191, China

    Juan Liu, Zhengju Chen, Dou Dou, Limei Liu, Xiaoxing Yu & Yuansheng Gao

  2. Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China

    Juan Liu, Zhengju Chen, Dou Dou, Limei Liu, Xiaoxing Yu & Yuansheng Gao

  3. Department of Pathophysiology, Liaoning Medical University, Jinzhou, Liaoning, China

    Liping Ye

  4. Department of Physiology, Heze Medical College, Shandong, China

    Huixia Liu

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  1. Juan Liu
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Correspondence to Yuansheng Gao.

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Liu, J., Chen, Z., Ye, L. et al. Preservation of nitric oxide-induced relaxation of porcine coronary artery: roles of the dimers of soluble guanylyl cyclase, phosphodiesterase type 5, and cGMP-dependent protein kinase. Pflugers Arch - Eur J Physiol 466, 1999–2008 (2014). https://doi.org/10.1007/s00424-014-1441-2

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  • DOI: https://doi.org/10.1007/s00424-014-1441-2

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