Protein kinase G regulates the basal tension and plays a major role in nitrovasodilator-induced relaxation of porcine coronary veins.
OBJECTIVE
Coronary venous activity is modulated by endogenous and exogenous nitrovasodilators. The present study was to determine the role of protein kinase G (PKG) in the regulation of the basal tension and nitrovasodilator-induced relaxation of coronary veins.


METHODS
Effects of a PKG inhibitor on the basal tension and responses induced by nitroglycerin, DETA NONOate, and 8-Br-cGMP in isolated porcine coronary veins were determined. Cyclic cGMP was measured with radioimmunoassay. PKG activity was determined by measuring the incorporation of 32P from gamma-32P-ATP into the specific substrate BPDEtide.


RESULTS
Rp-8-Br-PET-cGMPS, a specific PKG inhibitor, increased the basal tension of porcine coronary veins and decreased PKG activity. The increase in tension was 38% of that caused by nitro-L-arginine. Relaxation of the veins induced by nitroglycerin and DETA NONOate was accompanied with increases in cGMP content and PKG activity. These effects were largely eliminated by inhibiting soluble guanylyl cyclase with ODQ. The increase in PKG activity induced by the nitrovasodilators was abolished by Rp-8-Br-PET-cGMPS. The relaxation caused by these dilators and by 8-Br-cGMP at their EC50 was attenuated by the PKG inhibitor by 51-66%.


CONCLUSIONS
These results suggest that PKG is critically involved in nitric oxide-mediated regulation of the basal tension in porcine coronary veins and that it plays a primary role in relaxation induced by nitrovasodilators. Since nitric oxide plays a key role in modulating coronary venous activity, augmentation of PKG may be a therapeutic target for improving coronary blood flow.
Qi
H
H
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China.
Zheng
X
X
Qin
X
X
Dou
D
D
Xu
H
H
Raj
J U
JU
Gao
Y
Y
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D009569:Nitric Oxide / Q000494:pharmacology; D005996:Nitroglycerin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009924:Organ Culture Techniques; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011863:Radioimmunoassay; D013552:Swine; D013873:Thionucleotides / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*
D009603:Nitroso Compounds; D047428:Protein Kinase Inhibitors; D013873:Thionucleotides; D014665:Vasodilator Agents; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; C098740:8-bromo-beta-phenyl-1,N(2)-ethenoguanosine 3',5'-cyclic monophosphorothioate; D009569:Nitric Oxide; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D005996:Nitroglycerin; D006152:Cyclic GMP