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Intermittent Hypoxia in Rats Reduces Hydrogen Sulfide Activation of Large‐Conductance Ca2+‐Activated Potassium Channels in Mesenteric Arteries
Author(s) -
JacksonWeaver Olan,
Riddle Melissa A.,
Bosc Laura Gonzalez,
Paredes Daniel A.,
Walker Benjimen R.,
Kanagy Nancy L.
Publication year - 2011
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.25.1_supplement.643.13
Intermittent hypoxia‐induced hypertension in rats (IH) enhances myogenic tone in mesenteric arteries. This augmented myogenic tone is due to loss of hydrogen sulfide (H 2 S), a vasodilator produced by cystathionine γ‐lyase (CSE) from cysteine (Cys). Because H 2 S is a putative activator of BKCa channels, we hypothesized that augmented myogenic tone after IH is caused by reduced H 2 S activation of these channels resulting in vascular smooth muscle (VSM) depolarization. In constricted mesenteric arteries, dilation to Cys was less in IH than Sham arteries. Both the CSE inhibitor β cyano‐L‐alanine (BCA) and endothelial cell (EC) disruption reduced Cys‐induced dilation in Sham but not IH arteries. Dilation to the H 2 S donor NaHS was blocked in Sham and IH arteries by the BK Ca channel blocker iberiotoxin (IbTx) or by EC disruption. VSM membrane potential (E m ) was depolarized in IH compared to Sham arteries and depolarized by BCA only in the Sham group. NaHS hyperpolarized VSM cells in Sham and IH arteries. Because H 2 S effects required EC, BK Ca currents were recorded in freshly dispersed EC from Sham rats using whole cell patch clamp. EC BK Ca currents were reduced by CSE inhibition with BCA. These data suggest a novel signaling mechanism by which H 2 S activates EC BK Ca channels to promote vasodilation. Furthermore, IH exposure decreases activity of the CSE/H 2 S system, potentially contributing to sleep apnea‐induced hypertension. Research Support: HL82799 (NLK)