Intermittent Hypoxia in Rats Reduces Hydrogen Sulfide Dependent Dilation to Enhance Myogenic Tone in Mesenteric Arteries

Abstract

Sleep apnea is an independent risk factor for hypertension and rats exposed to intermittent hypoxia (IH) develop hypertension. We have shown that exposing rats for 14 days to IH enhances myogenic tone (MT) in small mesenteric arteries (MA) compared to MA from control (Sham) rats. Endothelial disruption enhanced MT in Sham arteries but had no effect in IH arteries. H2S is an endogenous vasodilator produced by cystathionine‐γ‐lyase (CSE) in the vasculature. We hypothesized that H2S produced by CSE in the endothelium reduces MT in MA from Sham rats and that H2S production in MA is impaired after 14 days of IH. Vessel wall [Ca2+]i and inner diameter were recorded in pressurized, fura‐2 loaded MA from IH and Sham rats. The CSE inhibitor β cyano L‐alanine (BCA) enhanced MT in Sham arteries compared to vehicle (20.2 ± 6.5% vs. 8.6 ± 1.0) and had no effect in IH arteries (24.0 ± 5.2 vs. 23.6 ± 7.9%). The H2S scavenger Bi(III) subsalicylate enhanced MT in Sham arteries similarly to BCA (20.4 ± 3.4%). NaHS (H2S donor) dilated both Sham and IH endothelium disrupted arteries (42.7 ± 5.7 vs. 57.5 ± 14.4%) with MT. These results suggest that H2S produced by CSE reduces MT in small endothelium intact MA and IH abolishes this effect of H2S. Dilation to NaHS is unaffected in IH endothelium disrupted arteries suggesting that enhanced MT is due to lower levels of endogenous H2S in MA.This work was supported by NIH grants HL82799 (NLK) and HL07736 (OJW).