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Regional heterogeneity in EDHF‐mediated relaxation in the rat mesenteric vascular bed: role of small‐ and intermediate conductance calcium‐activated K+ channels
Author(s) -
Hilgers Rob HP
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1113
Subject(s) - apamin , myograph , phenylephrine , mesenteric arteries , hyperpolarization (physics) , chemistry , endothelium derived hyperpolarizing factor , charybdotoxin , vasodilation , biophysics , thapsigargin , anesthesia , iberiotoxin , medicine , endocrinology , pharmacology , artery , potassium channel , calcium , stereochemistry , biology , blood pressure , nuclear magnetic resonance spectroscopy
Background Calcium‐activated K + ‐channels (K Ca ) are important regulators of vasomotor tone. Activation of these endothelial K Ca channels result in smooth muscle hyperpolarization and relaxation. The relative contribution of the EDHF‐mediated relaxation differs depending on the vessel type and size. It is unknown whether these K Ca channels are differentially distributed along the same vascular bed and hence have different roles in mediating the EDHF response. We therefore assessed the role of small‐ (SK Ca ) and intermediate‐ (IK Ca ) conductance K Ca channels in mediating EDHF‐induced relaxations in both 4 th and 1 st ‐order side branches of the rat superior mesenteric artery (MrA). Methods and Results 2‐mm segments of each MrA were mounted in the wire‐myograph, incubated with L‐NAME (100 μM) and indomethacin (INDO, 10 μM) and pre‐contracted with phenylephrine (10 μM). Cumulative concentration‐response curves to ACh (10 −9 –10 −5 M) were performed in the absence or presence of the selective SK Ca channel antagonist apamin (0.5 μM) or the selective IK Ca channel antagonist TRAM‐34 (10 μM). Maximal ACh‐induced relaxations in the presence of both L‐NAME and INDO were similar in both artery types (Emax 76±4% in 4 th ‐order versus 75±7% in 1 st ‐order MrA). Apamin almost completely abolished these relaxations in 4 th ‐order MrA (Emax 2±2 %), but only partially blocked relaxations in 1 st ‐order MrA (Emax 36±8%). TRAM‐34 caused a significantly greater inhibition of the ACh‐induced EDHF‐mediated relaxation in 4 th ‐order MrA compared to 1 st ‐order MrA (Emax 26±7% versus 57±8%, respectively). Conclusion Our data demonstrate regional heterogeneity in SK Ca and IK Ca function, and stress the importance of K Ca channels in smaller resistance‐sized arteries, where the role of EDHF is more pronounced.