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This Article Full Text Full Text (PDF) All Versions of this Article: 560/2/563    most recent jphysiol.2004.071399v2 jphysiol.2004.071399v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chan, A. K Articles by von der Weid, P.-Y. Search for Related Content PubMed PubMed Citation Articles by Chan, A. K Articles by von der Weid, P.-Y.

¹ Mucosal Inflammation Research Group
² Smooth Muscle Research Group
³ Diabetes & Endocrine Research Group
⁴ Department of Physiology & Biophysics
⁵ Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada

Lymphatic vessels rhythmically constrict to avoid fluid and protein accumulation in the interstitial space. This activity is critical during inflammation to prevent excessive oedema. Lymphatic pumping is intrinsic to the smooth muscle in the vessel wall and is due to the spontaneous occurrence of action potentials, the pacemaker of which is proposed to be spontaneous transient depolarizations (STDs). This function is highly susceptible to the fluid load and modulated by chemical agents, amongst which inflammatory mediators are important players. Activation of proteinase-activated receptors (PARs) has been involved in inflammation and affects vascular smooth muscle tone. The present study aims to investigate the role of PAR₂, a member of the PAR family, in lymphatic vessel pumping. RT-PCR experiments revealed that PAR₂ message is present in lymphatic vessels of the guinea-pig mesentery. Agonists of PAR₂ such as trypsin and the activating peptide, SLIGRL-NH₂, caused a decrease in the contractile activity of intraluminally perfused lymphatic vessels. Moreover, intracellular microelectrode recordings from isolated vessels revealed that PAR₂ activation hyperpolarized the lymphatic smooth muscle membrane potential and altered STD amplitude and frequency. The decreases in constriction frequency and STD activity as well as the hyperpolarization were dependent on a functional endothelium, not affected by NO synthase or guanylyl-cyclase inhibition, but mimicked by PGE₂ and iloprost and blocked by indomethacin (10 µM) and glibenclamide (1 µM). These results show that PAR₂ activation alters guinea-pig lymphatic vessel contractile and electrical activity via the production of endothelium-derived cyclo-oxygenase metabolites.

(Received 6 July 2004; accepted after revision 23 August 2004; first published online 26 August 2004)
Corresponding author P.-Y. von der Weid: Department of Physiology & Biophysics, Faculty of Medicine, University of Calgary, 3330 Hospital Drive N.W., Calgary, Alberta, Canada T2N 4N1. Email: vonderwe{at}ucalgary.ca

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