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cGMP-dependent protein kinase in regulation of basal tone and in nitroglycerin- and nitric-oxide-induced relaxation in porcine coronary artery

  • Cardiovascular System
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Abstract

Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) may act as a critical enzyme for nitric-oxide-induced vasodilation. In this study, the role of PKG in regulation of basal tension and in relaxation induced by nitrovasodilators in coronary arteries was determined. Under basal conditions, Rp-8-Br-PET-cGMPS, a specific PKG inhibitor, evoked a significant contraction of isolated porcine coronary arteries, which was prevented by nitro-l-arginine or the removal of the endothelium. Relaxation to nitroglycerin and (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA NONOate) in vessels preconstricted with U46619 was largely abolished by 1H-[1,2,4]oxadiazolo[4,3]quinoxalin-1-one (ODQ) and inhibited by 48 to 79% by Rp-8-Br-PET-cGMPS. Relaxation of the vessels to 8-Br-cGMP was inhibited by 56% by Rp-8-Br-PET-cGMPS. The basal activity of PKG but not that of cyclic adenosine monophosphate-dependent protein kinase (PKA) was inhibited by nitro-l-arginine, ODQ, or Rp-8-Br-PET-cGMPS. The activity of PKG but not that of PKA was increased by nitroglycerin and DETA NONOate in intact vessels and increased by cGMP in the tissue homogenates. These effects were abolished by Rp-8-Br-PET-cGMPS but not by myristoylated PKI, a specific inhibitor of PKA. These results suggest that in porcine coronary arteries, PKG is involved in the regulation of basal tension and plays a primary role in relaxation induced by nitrovasodilators, whereas PKA may play a minor role.

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Acknowledgments

This study was supported in part by the National Natural Science Foundation of China, Grant #30370523, #30470629, a Program for Changjiang Scholars and Innovative Research Team in University, the Major National Basic Research Program of the People’s Republic of China (No. 2006CB503802), and the National Institute of Health Grants HL-059435 and HL-075187, USA.

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  1. Department of Physiology and Pathophysiology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing, 100083, China

    Xue Qin, Xiaoxu Zheng, Hui Qi, Dou Dou & Yuansheng Gao

  2. Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, Beijing, China

    Yuansheng Gao

  3. Division of Neonatology, Harbor-UCLA Medical Center, Torrance, CA, USA

    J. Usha Raj

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  1. Xue Qin
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Correspondence to Yuansheng Gao.

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Qin, X., Zheng, X., Qi, H. et al. cGMP-dependent protein kinase in regulation of basal tone and in nitroglycerin- and nitric-oxide-induced relaxation in porcine coronary artery. Pflugers Arch - Eur J Physiol 454, 913–923 (2007). https://doi.org/10.1007/s00424-007-0249-8

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