title: 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.
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.
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing, 100191, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Zhengju
authors.initials: Z
authors.lastname: Chen
authors.forename: Liping
authors.initials: L
authors.lastname: Ye
authors.forename: Huixia
authors.initials: H
authors.lastname: Liu
authors.forename: Dou
authors.initials: D
authors.lastname: Dou
authors.forename: Limei
authors.initials: L
authors.lastname: Liu
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Yu
authors.forename: Yuansheng
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000737:chemistry / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009603:Nitroso Compounds / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D055503:Protein Multimerization; D011688:Purinones / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D013552:Swine; D014664:Vasodilation
chemical_list: C494582:1H-(1,2,3)oxadiazolo(4,4-a)quinoxalin-1-one; D009603:Nitroso Compounds; D010069:Oxadiazoles; D058986:Phosphodiesterase 5 Inhibitors; D047428:Protein Kinase Inhibitors; D011688:Purinones; D011810:Quinoxalines; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D009569:Nitric Oxide; D017869:Cyclic GMP-Dependent Protein Kinases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006162:Guanylate Cyclase; C011145:zaprinast