abstract
- Ca(2+) sparks are vascular smooth muscle cell (VSMC) Ca(2+)-release events that are mediated by ryanodine receptors (RyR) and that promote vasodilation by activating large-conductance 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 to 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/site while H2S increases in spark activity were due to increased spark sites/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.Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology.