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dc.contributor.advisorCruickshank, Stuart F.
dc.contributor.advisorWainwright, Cherry L.
dc.contributor.advisorMcCaig, Dorothy
dc.contributor.authorDospinescu, Ciprian
dc.date.accessioned2009-07-09T14:16:35Z
dc.date.available2009-07-09T14:16:35Z
dc.date.issued2009-03
dc.identifier.urihttp://hdl.handle.net/10059/380
dc.description.abstractIn the pulmonary circulation, alveolar hypoxia contributes to blood flow regulation. Hypoxic pulmonary vasoconstriction (HPV) involves both pulmonary arteries and veins, but little is known of the contractile mechanisms specific to the veins. The aim of these studies was to examine the hypoxic response in small porcine intrapulmonary veins in relation to the arterial response, and investigate the effects of hypoxia on ion conductances in single myocytes from intrapulmonary veins. In wire myography experiments, intrapulmonary veins contracted more than sizematched arteries in response to hypoxia and agonists KCl and PGF2α. Venous contractions were inhibited by removal of extracellular Ca2+ or in the presence of Clchannel blocker NFA, effects not seen in the arteries. To examine the mechanisms of venous contraction at cellular level, single pulmonary vein smooth muscle cells (PVSMC) were freshly isolated and characterised morphologically and electrophysiologically for the first time. In patch-clamp studies, hypoxia reversibly inhibited a whole-cell outward current in the presence of BKCa channel antagonist Penitrem A. By subtracting currents recorded in normoxia and hypoxia, a novel hypoxia-sensitive K+ current (IK(H)) was revealed in PVSMC. IK(H) was a rapidly activating, partially inactivating current and was sensitive to KV channel blocker 4-AP. The biophysical properties of IK(H) revealed the voltage window of current availability with a peak near the resting membrane potential of PVSMC. In conclusion, these findings highlight differences between the contractile properties of veins and arteries and reveal a significant contribution of Ca2+ influx and an NFA-sensitive conductance during venous contraction to agonists and hypoxia. Furthermore, the results suggest that a novel hypoxia-sensitive KV current contributes to membrane potential under resting conditions in PVSMC and its inhibition by hypoxia may contribute to the initiation of HPV in porcine intrapulmonary veins.en
dc.description.sponsorshipRobert Gordon University (RDI studentship plus overseas research student award scheme) Ratiu Foundation Uk. Mrs Ramona Mitrica Boehringer Ingelheim Foundation The Physiological Societyen
dc.format.extent4475221 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoenen
dc.publisherThe Robert Gordon Universityen
dc.relationDOSPINESCU, C. and CRUICKSHANK, S. F., 2006. [cL-]o and [Ca2+]o affect hypoxia-induced contractions differently in porcine intrapulmonary arteries and veins. In: Abstracts, The Physiological Society workshop on Cardiopulmonary Function in Health and Dieease, Prague, The Czech Republic)en
dc.relationDOSPINESCU, C. and CRUICKSHANK, S. F., 2006. Cl- channel blocker NFA inhibits PGF2a and hypoxia-induced contractions in porcine intrapulmonary veins but not in arteries. In: Absrracts, FASEB Summer Research Conference, Smooth Muscle, Snowmass Village, Colorado, USA.en
dc.relationDOSPINESCU, C., MCCAIG, D., WAINWRIGHT, C. L. and CRUICKSHANK, S. F., 2006. Different role for [Cl-]o in hypoxia induced contractions of small intrapulmonary arteries and veins. In: Journal of Molecular and Cellular Cardiology, 40 (6), pp. 1015.en
dc.relationDOSPINESCU, C., YAMAWAKI, N., MCCAIG, D., WAINWRIGHT, C. L. and CRUICKSHANK, S. F., 2005. Low chloride potentiation of hypoxic pulmonary vasoconstriction. In: Journal of Physiology 568P:PC44.en
dc.rightsCopyright : Ciprian Dospinescu.en
dc.subjectHypoxic pulmonary vasoconstrictionen
dc.subjectHPVen
dc.subjectHypoxiaen
dc.subjectPulmonary circulationen
dc.titleCellular mechanisms of acute hypoxic pulmonary vasoconstriction in intrapulmonary veins.en
dc.typeTheses and dissertationsen
dc.publisher.departmentSchool of Pharmacy and Life Sciencesen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhDen


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