title: Intermittent hypoxia in rats reduces activation of Ca2+ sparks in mesenteric arteries.
abstract: Ca(+) sparks are vascular smooth muscle cell (VSMC) Ca(2+)-release events that are mediated by ryanodine receptors (RyR) and promote vasodilation by activating large-conductance Ca(2+)-activated potassium channels and inhibiting myogenic tone. We have previously reported that exposing rats to intermittent hypoxia (IH) to simulate sleep apnea augments myogenic tone in mesenteric arteries through loss of hydrogen sulfide (H2S)-induced dilation. Because we also observed that H2S can increase Ca(2+) spark activity, we hypothesized that loss of H2S after IH exposure reduces Ca(2+) spark activity and that blocking Ca(2+) spark generation reduces H2S-induced dilation. Ca(2+) spark activity was lower in VSMC of arteries from IH compared with sham-exposed rats. Furthermore, depolarizing VSMC by increasing luminal pressure (from 20 to 100 mmHg) or by elevating extracellular [K(+)] increased spark activity in VSMC of arteries from sham rats but had no effect in arteries from IH rats. Inhibiting endogenous H2S production in sham arteries prevented these increases. NaHS or phosphodiesterase inhibition increased spark activity to the same extent in sham and IH arteries. Depolarization-induced increases in Ca(2+) spark activity were due to increased sparks per site, whereas H2S increases in spark activity were due to increased spark sites per cell. Finally, inhibiting Ca(2+) spark activity with ryanodine (10 μM) enhanced myogenic tone in arteries from sham but not IH rats and blocked dilation to exogenous H2S in arteries from both sham and IH rats. Our results suggest that H2S regulates RyR activation and that H2S-induced dilation requires Ca(2+) spark activation. IH exposure decreases endogenous H2S-dependent Ca(2+) spark activation to cause membrane depolarization and enhance myogenic tone in mesenteric arteries.
authors.affiliation: Vascular Physiology Group, Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Olan
authors.initials: O
authors.lastname: Jackson-Weaver
authors.affiliation: Vascular Physiology Group, Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Osmond
authors.affiliation: Vascular Physiology Group, Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Jay S
authors.initials: JS
authors.lastname: Naik
authors.affiliation: Vascular Physiology Group, Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Laura V
authors.initials: LV
authors.lastname: Gonzalez Bosc
authors.affiliation: Vascular Physiology Group, Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Benjimen R
authors.initials: BR
authors.lastname: Walker
authors.affiliation: Vascular Physiology Group, Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico nkanagy@salud.unm.edu.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Kanagy
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D004195:Disease Models, Animal; D006862:Hydrogen Sulfide / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D008638:Mesenteric Arteries / Q000378:metabolism / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism; D013440:Sulfides / Q000378:metabolism / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D010726:Phosphodiesterase Inhibitors; D019837:Ryanodine Receptor Calcium Release Channel; D013440:Sulfides; D014665:Vasodilator Agents; C025451:sodium bisulfide; D006862:Hydrogen Sulfide
keywords: endothelium; myogenic tone; ryanodine receptors; sleep apnea; vascular smooth muscle