Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/27754
- Title
- ET-1-associated vasomotion and vasospasm in lymphatic vessels of the guinea-pig mesentery
- Author/Creator
-
Zhao, Jun;
van Helden, Dirk F.
- Description
- 1 In vitro experiments were performed to investigate the actions of endothelin-1 (ET-1) on vasomotion and vasospasm in guinea-pig mesenteric lymphatics. 2 ET-1 modulated lymphatic vasomotion independent of the endothelium, with lower concentrations (≤10 nM) increasing lymphatic vasomotion and higher concentrations (≥100 nM) causing vasospasm. 3 ET-1-induced increases in vasomotion were accompanied by an increase in tonic [Ca²⁺]{subscript i}. 4 These actions were inhibited by the ET{subscript A} receptor antagonist BQ-123 (1 µM), the phospholipase C (PLC) inhibitor U73122 (5 µM), removal of extracellular Ca²⁺, chelation of intracellular Ca²⁺ with BAPTA/AM (10 µM), the store Ca²⁺-ATPase inhibitor thapsigargin (1 µM), caffeine (10 mM) and the inositol 1,4,5-trisphosphate (IP₃) receptor blocker heparin and 2-APB (30 µM). In contrast, the ET{subscript B} receptor antagonist BQ-788 (1 µM), ryanodine (1 & 20 µM), pertussis toxin (PTx) or Cs⁺ had no significant actions on vasomotion or the magnitude of increase in tonic [Ca²⁺]{subscript i}. 5 ET-1-induced vasospasm was accompanied by a transient increase in smooth muscle [Ca²⁺]{subscript i} followed by a sustained plateau, an action that was abolished by removal of extracellular Ca²⁺, but only marginally inhibited by nifedipine (1 µM). 6 Caffeine (10 mM), SKF 96165 (30 µM) or U73122 (5 µM) together with nifedipine (1 µM) abolished ET-1-induced vasospasm and increase in [Ca²⁺]{subscript i}. 7 These results indicate that ET-1 increases lymphatic vasomotion by acting on smooth muscle ET{subscript A} receptors and activation of G-protein-PLC-IP₃ cascade, which is known to cause pacemaker Ca²⁺ release and resultant pacemaker potentials. High concentrations of ET-1 cause a failure in Ca²⁺ homeostasis causing vasospasm, triggered by excessive Ca²⁺ influx primarily through store-operated channels (SOCs) with L-Ca²⁺ voltage-operated channels (VOCs) also contributing, but to a much lesser extent.
- Relation
- British Journal of Pharmacology Vol. 140, Issue 8, p. 1399-1413
- Publisher Link
- http://dx.doi.org/10.1038/sj.bjp.0705573
- Date
- 2003
- Publisher
- Nature Publishing Group
- Keyword(s)
-
endothelin-1;
lymphatics;
Ca²⁺ release;
Ca²⁺ influx;
vasomotion;
vasospasm
- Resource Type
- journal article
- Identifier
- http://hdl.handle.net/1959.13/27754
- Identifier
- ISSN:0007-1188
- Reviewed
10 Visitors
11 Hits
0 Downloads
List Of Titles
