Loss of Hydrogen Sulfide‐Stimulated Ca 2+ Spark Activity in Arteries from Rats with Intermittent Hypoxia‐Induced Hypertension

Obstructive sleep apnea (OSA) is a risk factor for hypertension. Previous studies from our laboratory demonstrate increased blood pressure and increased myogenic vascular tone in mesenteric arteries from rats exposed to intermittent hypoxia (IH), a model of OSA. We have also observed that hydrogen sulfide (H 2 S) activates Ca 2+ sparks in mesenteric arteries, and that IH exposure in rats decreases H 2 S‐dependent dilation in mesenteric arteries. Therefore, we hypothesized that IH exposure would decrease H 2 S‐activated Ca 2+ spark activity in mesenteric arteries to augment vasoconstriction. Mesenteric arteries collected from male Sprague‐Dawley rats exposed to IH (20 exposures/hr of 5% O 2 /5% CO 2 7 hr/day for 14 days) were loaded with the Ca 2+ indicators fluo‐4 AM and Oregon Green BAPTA‐1 and then cannulated and pressurized to 75 mmHg. Basal Ca 2+ spark activity was decreased in arteries from IH rats (0.31±0.04 vs. 0.43±0.02 sparks/cell/sec in Sham). The inhibitor of H 2 S synthesis (beta cyanoalanine, BCA) decreased spark activity activity in Sham arteries te abolish this diffference. Vascular smooth muscle cell (VSMC) depolarization induced by elevating extracellular [K + ] or by increasing luminal pressure) increased Ca 2+ spark activity in arteries from Sham but not IH rats and this increase in Ca 2+ spark activity was prevented by removing the endothelium or by incubating with BCA. Ryanodine (10 µM) eliminated basal Ca 2+ spark activity and prevented both H 2 S‐induced dilation and H 2 S‐induced spark activation. Our results provide evidence of impaired H 2 S‐induced Ca 2+ spark regulation of vascular reactivity in a rodent model of OSA and point to this pathway as a target for blood pressure control in hypertensives.