cGMP-dependent protein kinase in regulation of basal tone and in nitroglycerin- and nitric-oxide-induced relaxation in porcine coronary artery |
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Authors: | Xue Qin Xiaoxu Zheng Hui Qi Dou Dou J Usha Raj Yuansheng Gao |
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Institution: | (1) Department of Physiology and Pathophysiology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing, 100083, China;(2) Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, Beijing, China;(3) Division of Neonatology, Harbor-UCLA Medical Center, Torrance, CA, USA |
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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]oxadiazolo4,3]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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Keywords: | cGMP Basal tension Relaxation Rp-8-Br-PET-cGMPS Myristoylated PKI |
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