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NO can suppress myogenic tone in rat middle cerebral arteries by activating BK Ca
Author(s) -
McNeish Alister James,
Dora Kim,
Garland Chris
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-b
Subject(s) - iberiotoxin , vasoconstriction , vasomotion , myograph , depolarization , cerebral arteries , vascular smooth muscle , myogenic contraction , channel blocker , chemistry , electrical impedance myography , medicine , biophysics , anatomy , nitric oxide , endocrinology , vasodilation , biology , calcium , smooth muscle
Aim In rat middle cerebral arteries myogenic tone is normally suppressed by a basal release of NO as inhibition of nitric oxide synthase (NOS) causes both vasoconstriction and smooth muscle depolarization associated with oscillations in tension and membrane potential (vasomotion). We wished to characterise the cellular mechanisms which underpin the vasoconstrictor effect of inhibitors of NOS by simultaneously measuring smooth muscle cell (SMC) membrane potential and tension or SMC [Ca 2+ ] and tension Methods Segments of the middle cerebral artery from male Wistar rats were mounted in a wire myograph. SMC membrane potential (E m ) was recorded with sharp glass microelectrodes. SMC [Ca 2+ ] was recorded on a confocal microscope with vessels loaded with fluo‐4. Results Inhibition of NOS with L‐NAME caused SMC depolarization associated with constriction and the development of vasomotion temporally linked to SMC [Ca2+]. This effect was mimicked by the blocker of guanylyl cyclase, ODQ and the BK Ca blocker, iberiotoxin. Relaxation and hyperpolarization produced by the NO donor DEA‐NONOate was inhibited by iberiotoxin. L‐NAME‐induced constriction and oscillations in SMC [Ca 2+ ] were abolished by the L‐type Ca channel inhibitor, nifedipine. Discussion In rat middle cerebral arteries inhibition of NOS with L‐NAME induces vasoconstriction and depolarization involving the entry of Ca 2+ . L‐NAME also induces vasomotion which is underpinned by oscillations in E m and SMC [Ca 2+ ]. Blockade of BK Ca mimics the effects of L‐NAME suggesting that NO normally suppresses myogenic tone by activation of SMC BK Ca channels. Supported by the British Heart Foundation