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

Abstract

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 (H2S) activates Ca2+ sparks in mesenteric arteries, and that IH exposure in rats decreases H2S-dependent dilation in mesenteric arteries. Therefore, we hypothesized that IH exposure would decrease H2S-activated Ca2+spark activity in mesenteric arteries to augment vasoconstriction. Mesenteric arteries collected from male Sprague-Dawley rats exposed to IH (20 exposures/hr of 5% O2/5% CO2 7 hr/day for 14 days) were loaded with the Ca2+indicators fluo-4 AM and Oregon Green BAPTA-1 and then cannulated and pressurized to 75 mmHg. Basal Ca2+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 H2S 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 Ca2+ spark activity in arteries from Sham but not IH rats and this increase in Ca2+ spark activity was prevented by removing the endothelium or by incubating with BCA. Ryanodine (10 µM) eliminated basal Ca2+ spark activity and prevented both H2S-induced dilation and H2S-induced spark activation. Our results provide evidence of impaired H2S-induced Ca2+ 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.