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Electromechanical and pharmacomechanical signalling pathways for conducted vasodilatation along endothelium of hamster feed arteries
Author(s) -
Domeier Timothy L.,
Segal Steven S.
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.124529
Subject(s) - vasodilation , hamster , endothelium , signalling , cardiology , medicine , chemistry , microbiology and biotechnology , anatomy , endocrinology , biology
Conducted vasodilatation (CVD) reflects the initiation and rapid (>mm s −1 ) spread of hyperpolarization along the endothelium and into smooth muscle. The ion channels that initiate CVD remain unclear as do signalling pathways that may complement electromechanical relaxation. Using isolated pressurized (75 mmHg; 37°C) feed arteries ( n = 63; diameter: rest: 53 ± 2 μm, maximal: 98 ± 2 μm) from hamster retractor skeletal muscle, we investigated the contribution of calcium‐activated potassium channels (K Ca ) and endothelium‐derived autacoids to CVD. Local delivery (1 μm micropipette tip; 500–2000 ms pulse) of acetylcholine (ACh) at the downstream end initiated a local increase in endothelial cell [Ca 2+ ] i (Fura‐PE3; Δratio 340/380 nm = 0.215 ± 0.032) that preceded CVD along the entire vessel. During local perifusion with K Ca antagonists, iberiotoxin (5 μ m ) had no effect, but charybdotoxin (CTX, 5 μ m ) + apamin (APA, 10 μ m ) abolished CVD reversibly. Remarkably, this local inhibition of K Ca unmasked a ‘slow‐conducted vasodilatation’ (SCVD) that spread >1200 μm at ∼21 μm s −1 ( n = 27). Recorded 500 μm upstream from the ACh stimulus, a rise in endothelial cell [Ca 2+ ] i (Δratio 340/380 nm) = 0.146 ± 0.017; P < 0.05) preceded SCVD (Δdiameter = 14 ± 3 μm) by ∼10 s. Before K Ca inhibition, antagonism of nitric oxide synthase ( N ω ‐nitro‐ l ‐arginine, 250 μ m ; l ‐NNA) and cyclooxygenase (indomethacin, 5 μ m ; INDO) had no effect on the amplitude of CVD yet response duration decreased by one‐third ( P < 0.05). During local CTX + APA perifusion, l ‐NNA + INDO abolished SCVD while conducted [Ca 2+ ] i responses remained intact. Thus, ACh triggers electromechanical relaxation of smooth muscle cells along the vessel initiated by local K Ca , and the ensuing ‘wave’ of Ca 2+ along the endothelium releases autacoids to promote pharmacomechanical relaxation.