Gap junctions support the sustained phase of hypoxic pulmonary vasoconstriction by facilitating calcium sensitization
| Autor: | Jeremy P.T. Ward, Ievgen V. Strielkov, Igor V. Kizub, Silke Becker, Jesus Prieto-Lloret, Anatoly Soloviev, Yasin Shaifta, Philip I. Aaronson, Vladimir A. Snetkov |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Calcium Channels L-Type Physiology Prostaglandin Blood Pressure Pulmonary Artery Pharmacology Diltiazem chemistry.chemical_compound Ca2+ sensitization Protein Phosphatase 1 Physiology (medical) Hypoxic pulmonary vasoconstriction medicine 18β-glycyrrhetinic acid Animals Rho kinase Channel blocker Phosphorylation Rats Wistar Hypoxia Rho-associated protein kinase Gap junctions Sensitization rho-Associated Kinases Chemistry hypoxic pulmonary vasoconstriction Gap Junctions Original Articles Integrative Physiology and Pathophysiology Hypoxia (medical) Calcium Channel Blockers Rats medicine.anatomical_structure Vasoconstriction Anesthesia Glycyrrhetinic Acid Calcium medicine.symptom Cardiology and Cardiovascular Medicine Signal Transduction medicine.drug Myograph |
| Zdroj: | Kizub, I V, Strielkov, I V, Shaifta, Y, Becker, S, Prieto-Lloret, J, Snetkov, V A, Soloviev, A I, Aaronson, P I & Ward, J P T 2013, ' Gap junctions support the sustained phase of hypoxic pulmonary vasoconstriction by facilitating calcium sensitization ', Cardiovascular Research, vol. 99, no. 3, pp. 404-411 . https://doi.org/10.1093/cvr/cvt129 Cardiovascular Research |
| ISSN: | 1755-3245 0008-6363 |
| DOI: | 10.1093/cvr/cvt129 |
| Popis: | Aims: To determine the role of gap junctions (GJ) in hypoxic pulmonary vasoconstriction (HPV).Methods and results: Studies were performed in rat isolated intrapulmonary arteries (IPA) mounted on a myograph, and in anesthetized rats. Hypoxia induced a biphasic HPV response in IPA preconstricted with prostaglandin F2α (PGF2α, 3 µM) or 20 mM K+. The GJ inhibitors 18β-glycyrrhetinic acid (18β-GA, 30 µM), heptanol (3.5 mM) or 2-aminoethoxydiphenyl borate (2-APB) (75 µM) had little effect on the transient phase 1 of HPV, but abolished the sustained phase 2 which is associated with Ca2+ sensitisation. The voltage-dependent Ca2+ channel blocker diltiazem (10 µM) had no effect on HPV, and did not alter the inhibitory action of 18β-GA. Sustained HPV is enhanced by high glucose (15 mM) via potentiation of Ca2+ sensitization; in the presence of high glucose 18β-GA still abolished sustained HPV. Simultaneous measurement of tension and intracellular Ca2+ using Fura PE-3 demonstrated that whilst 18β-GA abolished tension development during sustained HPV, it did not affect the elevation of intracellular Ca2+. Consistent with this, 18β-GA abolished hypoxia-induced phosphorylation of the Rho kinase target MYPT-1. In anaesthetized rats hypoxia caused a biphasic increase in systolic right ventricular pressure. Treatment with oral 18β-GA (25 mg/kg) abolished the sustained component of the hypoxic pressor response.Conclusion: These results imply that GJs are critically involved in the signalling pathways leading to Rho kinase-dependent Ca2+ sensitization during sustained HPV, but not elevation of intracellular Ca2+, and may explain the dependence of the former on an intact endothelium. |
| Databáze: | OpenAIRE |
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