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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2009; 55(6): 63-68

HYPOXIC PULMONARY HYPERTENSION: THEROLE OF PHOSPHATIDYLCHOLINE-SPECIFICHYPOXIC PULMONARY HYPERTENSION: THE ROLE OF PHOSPHATIDYLCHOLINE-SPECIFIC PHOSPHOLIPASE C

Z.A.gorenko, L.S.karbovska, Sepideh Parchami Ghazaee Mehdi, I.A.lukyanenko,S.P.veselsky

    ДУ “Ін-т фармакології та токсикології АМНУкраїни”; Київ



Abstract

The aim of the study was to investigate the role of phosphati-dylcholine-specific phospholipase C (PC-PLC) in the deve­lopment of hypoxic pulmonary hypertension. Induction of hypoxic hypoxia in rats resulted in a biphasic increase in sys­tolic right ventricular pressure (RVP). The first phase was transient (5.4 ± 0,9 min), while the second phase was sus­tained and persisted during the whole time course of hypoxia (120 min). An inhibition of cNOS with L-NAME (25 mg/kg; i/v) did not cause any change in the nature of the hypoxic reaction, despite the RVP values were significantly higher in normoxia and hypoxia. These results demonstrate that NO synthase is not substantially involved in the hypoxic pulmo­nary vasoconstriction. Injection of PKC inhibitor chelerythrine (0.5 mg/kg; i/v) prevented the development of the first phase of the RVP increase and reduced the second phase by 40%. An inhibition of PC-PLC with D609 (5 mg/kg; i/v) completely abolished pulmonary hypertension. The results obtained sug­gest that PC-PLC possibly plays a key role in the develop­ment and maintenance of hypoxic pulmonary hypertension.

Full text: (PDF, in Ukrainian)

References

  1. Закон України № 3447-IV “Про захист тварин від жорстокого поводження” // Відомості Верховної Ради України. - 2006. - № 27. - С 230.
  2. Каро К., Педли Т., Шротер Р., Сид У Механика кровообращения. - М.: Мир, 1981. - 624 с3. Коваленко Е.А., Березовский В.А., Эпштейн И.М. Полярографическое определив кислорода в организме. - М.: Медицина, 1975. - 231 с.
  3. Barman S. A. Effect of protein kinase C inhibition on hypoxic pulmonary vasoconstriction // Amer. J. Physiol. Lung Cell Mol. Physiol. - 2001. - 280. -P. L888-L895.
  4. Barnett R. L., Ruffini L., Ramsammy L. et al. Nord cGMP antagonizes angiotensin-mediated phosphati­dylcholine hydrolysis and C kinase activation in mesangial cells // Amer. J. Physiol. Cell Physiol. - 1995. -268,№2. - P. C376-C38.
  5. Cheng Y., Zhao Q., Liu X. et al. Phosphatidylcholine-specific phospholipase C, p53 and ROS in the associa­tion of apoptosis and senescence in vascular endothelial cells // FEBS Lett. - 2006. - 580, №20. - P. 4911-4915.
  6. European convention for the protection of vertebrate animals used for experimental and other scientific pur­poses. - Council of Europe, Strasbourg, 1986. - 53 p.
  7. Goldberg M., Zhang H.L., Steinberg S.F. Hypoxia al­ters the subcellular distribution of protein kinase C isoforms in neonatal rat ventricular myocytes // J. Clin. Invest. - 1997. - 99, №1. - P. 55-61.
  8. 9. Greenberg B., Kishiyama S. Endothelium-dependent and -independent responses to severe hypoxia in rat pulmonary artery // Amer. J. Physiol. Heart Circ. Physiol. - 1994. - 265. - P. H1712-H1720.
  9. 10. Karamsetty V.S., MacLean M.R., McCulloch K.M. Hypoxic constrictor response in the isolated pulmo­nary artery from chronically hypoxic rats // Respir. Physiol. - 1996. - 105. - P. 85-93.
  10. Leach R.M., Robertson T.P., Twort C.H.C., Ward J.P.T. Hypoxic vasoconstriction in rat pulmonary and mesenteric arteries // Amer. J. Physiol. Lung Cell Mol. Physiol. - 1994. - 266. - P. L223-L231.
  11. Littler C.M., Morris K.G., Fagan K.A. et al. Protein kinase C-epsilon-null mice have decreased hypoxic pulmonary vasoconstriction // Amer. J. Physiol. Heart Circulat. Physiol. - 2003. - 284. - P. H1321-H1331.
  12. Liu G.L., Shaw L., Heagerty A.M. et al. Endothelin-1 stimulates hydrolysis of phosphatidylcholine by phos-pholipases C and D in intact rat mesenteric arteries // J. Vasc. Res. - 1999. - 36. - №1. - P.35-46.
  13. Liu H., Zhang H., Forman H.J. Silica Induces Mac­rophage Cytokines through Phosphatidylcholine-Spe-cific Phospholipase C with Hydrogen Peroxide // Amer. J. Resp. Cell Mol. Biol. - 2007. - 36. - P. 594-599.
  14. Robertson T.P., Aaronson P.I., Ward J.P.T. Hypoxic vaso­constriction and intracellular Ca2+ in pulmonary arteries: evidence for PKC-independent Ca2+ sensitization // Amer. J. Physiol. - 1995. - 268. - P. H301-H307.
  15. Robertson T.P., Aaronson P.I., Ward J.P.T. Ca2+ sen­sitization during sustained hypoxic pulmonary vaso­constriction is endothelium dependent // Amer. J. Physiol. Lung Cell Mol. Physiol. - 2003. - 284, №6. -P. L1121-L1126.
  16. Salameh G., Karamsetty M.R., Warburton R.R. et al. Differences in acute hypoxic pulmonary vasorespon-siveness between rat strains: role of endothelium // J. Appl. Physiol. - 1999. - 87. - P. 356-362.
  17. Ward J.P.T, Knock G.A., Snetkov V.A., Aaronson P.I. Protein kinases in vascular smooth muscle tone - role in the pulmonary vasculature and hypoxic pulmonary vasoconstriction // Pharmacol. and Therap. - 2004. -104. - P. 207-231.
  18. 19. Ward J.P.T., Snetkov V.A., Aaronson P.I. Calcium, mi­tochondria and oxygen sensing in the pulmonary circu­lation // Cell Calcium. - 2004. - 36. - P. 209-220.
  19. 20. Witzenrath M., Ahrens B., Kube1 S.M. et al. Allergic lung inflammation induces pulmonary vascular hyperresponsiveness // Eur. Respir. J. - 2006(Mar). -28. -P. 370-377.
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