Effect of oxygen on cyclic GMP-dependent protein kinase-mediated relaxation in ovine fetal pulmonary arteries and veins.

Abstract

Cyclic GMP-dependent protein kinase (PKG) plays an important role in regulating pulmonary vasomotor tone in the perinatal period. In this study, we tested the hypothesis that a change in oxygen tension affects PKG-mediated pulmonary vasodilation. Isolated intrapulmonary arteries and veins of near-term fetal lambs were first incubated for 4 h under hypoxic and normoxic conditions (Po2 of 30 and 140 mmHg, respectively) and then contracted with endothelin-1. 8-Bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP), a cell membrane-permeable analog of cGMP, induced a greater relaxation in vessels incubated in normoxia than in hypoxia. beta-Phenyl-1,N2-etheno-8-bromoguanosine-3',5'-cyclic monophosphorothioate, Rp isomer (Rp-8-Br-PET-cGMPS), a selective inhibitor of PKG, attenuated relaxation induced by 8-BrcGMP (10-4 and 3 x 10-4 M). In the presence of Rp-8-Br-PET-cGMPS, the differential responses to 8-BrcGMP between hypoxia and normoxia treatment were abolished in veins but not in arteries. cGMP-stimulated PKG activity was present in arteries but not in veins after 4 h of hypoxia. Both vessel types showed significant increase in cGMP-stimulated PKG activity after 4 h of normoxia. PKG protein (Western blot analysis) and PKG mRNA levels (quantitative RT-PCR) were greater in veins but not in arteries after 4-h exposure to normoxia vs. hypoxia. These results demonstrate that oxygen augments cGMP-mediated vasodilation of fetal pulmonary arteries and veins. Furthermore, the effect of oxygen on response of the veins to cGMP is due to an increase in the activity, protein level, and mRNA of PKG.

• Authors: Yuansheng Gao, Srinivas Dhanakoti, Earleen M Trevino, Fred C Sander, Ada M Portugal, J Usha Raj
• Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 285 Issue 3 Pg. L611-8 (Sep 2003) ISSN: 1040-0605 [Print] United States
• PMID: 12754191 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• RNA, Messenger
• Cyclic GMP-Dependent Protein Kinases
• Cyclic GMP
• Oxygen

Topics

• Animals
• Cyclic GMP (metabolism)
• Cyclic GMP-Dependent Protein Kinases (genetics, metabolism)
• Female
• Gene Expression Regulation, Developmental
• Gene Expression Regulation, Enzymologic
• Male
• Oxygen (pharmacology)
• Pregnancy
• Pulmonary Artery (embryology, physiology)
• Pulmonary Circulation (drug effects, physiology)
• Pulmonary Veins (embryology, physiology)
• RNA, Messenger (analysis)
• Sheep
• Vasodilation (drug effects, physiology)