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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.

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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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          Author and article information

          Journal
          Pflugers Arch.
          Pflugers Archiv : European journal of physiology
          0031-6768
          0031-6768
          Sep 2007
          : 454
          : 6
          Affiliations
          [1 ] Department of Physiology and Pathophysiology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing, 100083, China.
          Article
          10.1007/s00424-007-0249-8
          17377806
          f85b3d6e-cbf1-4b62-b2b4-cdc719ae149a
          History

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