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Simulated sleep apnea alters hydrogen sulfide regulation of blood flow and pressure.
Am J Physiol Heart Circ Physiol. 2021 02 01; 320(2):H511-H519.AJ

Abstract

In sleep apnea, airway obstruction causes intermittent hypoxia (IH). In animal studies, IH-dependent hypertension is associated with loss of vasodilator hydrogen sulfide (H2S), and increased H2S activation of sympathetic nervous system (SNS) activity in the carotid body. We previously reported that inhibiting cystathionine γ-lyase (CSE) to prevent H2S synthesis augments vascular resistance in control rats. The goal of this study was to evaluate the contribution of IH-induced changes in CSE signaling to increased blood pressure and vascular resistance. We hypothesized that chronic IH exposure eliminates CSE regulation of blood pressure (BP) and vascular resistance. In rats instrumented with venous catheters, arterial telemeters, and flow probes on the main mesenteric artery, the CSE inhibitor dl-propargylglycine (PAG, 50 mg/kg/day i.v. for 5 days) increased BP in Sham rats but decreased BP in IH rats [in mmHg, Sham (n = 11): 114 ± 4 to 131 ± 6; IH (n = 8): 131 ± 8 to 115 ± 7 mmHg, P < 0.05]. PAG treatment increased mesenteric vascular resistance in Sham rats but decreased it in IH rats (day 5/day 1: Sham: 1.50 ± 0.07; IH: 0.85 ± 0.19, P < 0.05). Administration of the ganglionic blocker hexamethonium (to evaluate SNS activity) decreased mesenteric resistance in PAG-treated Sham rats more than in saline-treated Sham rats or PAG-treated IH rats. CSE immunoreactivity in IH carotid bodies compared with those from Sham rats. However, CSE staining in small mesenteric arteries was less in arteries from IH than in Sham rats but not different in larger arteries (inner diameter > 200 µm). These results suggest endogenous H2S regulates blood pressure and vascular resistance, but this control is lost after IH exposure with decreased CSE expression in resistance size arteries. IH exposure concurrently increases carotid body CSE expression and relative SNS control of blood pressure, suggesting both vascular and carotid body H2S generation contribute to blood pressure regulation.NEW & NOTEWORTHY These results suggest that CSE's protective role in the vasculature is impaired by simulated sleep apnea, which also upregulates CSE in the carotid body. Thus, this enzyme system can exert both pro- and antihypertensive effects and may contribute to elevated SNS outflow in sleep apnea.

Authors+Show Affiliations

Vascular Physiology Group, Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico.Vascular Physiology Group, Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico.Vascular Physiology Group, Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico.Vascular Physiology Group, Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico.Vascular Physiology Group, Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico.Vascular Physiology Group, Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico.Vascular Physiology Group, Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico.Vascular Physiology Group, Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico.Vascular Physiology Group, Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33275519

Citation

Barrera, Adelaeda, et al. "Simulated Sleep Apnea Alters Hydrogen Sulfide Regulation of Blood Flow and Pressure." American Journal of Physiology. Heart and Circulatory Physiology, vol. 320, no. 2, 2021, pp. H511-H519.
Barrera A, Morales-Loredo H, Garcia JM, et al. Simulated sleep apnea alters hydrogen sulfide regulation of blood flow and pressure. Am J Physiol Heart Circ Physiol. 2021;320(2):H511-H519.
Barrera, A., Morales-Loredo, H., Garcia, J. M., Fregoso, G., Pace, C. E., Mendiola, P. J., Naik, J. S., Gonzalez Bosc, L. V., & Kanagy, N. L. (2021). Simulated sleep apnea alters hydrogen sulfide regulation of blood flow and pressure. American Journal of Physiology. Heart and Circulatory Physiology, 320(2), H511-H519. https://doi.org/10.1152/ajpheart.00672.2019
Barrera A, et al. Simulated Sleep Apnea Alters Hydrogen Sulfide Regulation of Blood Flow and Pressure. Am J Physiol Heart Circ Physiol. 2021 02 1;320(2):H511-H519. PubMed PMID: 33275519.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simulated sleep apnea alters hydrogen sulfide regulation of blood flow and pressure. AU - Barrera,Adelaeda, AU - Morales-Loredo,Humberto, AU - Garcia,Joshua M, AU - Fregoso,Gisel, AU - Pace,Carolyn E, AU - Mendiola,Perenkita J, AU - Naik,Jay S, AU - Gonzalez Bosc,Laura V, AU - Kanagy,Nancy L, Y1 - 2020/12/04/ PY - 2020/12/5/pubmed PY - 2021/2/20/medline PY - 2020/12/4/entrez KW - blood flow KW - carotid body KW - cystathionine γ-lyase KW - intermittent hypoxia KW - mesenteric arteries SP - H511 EP - H519 JF - American journal of physiology. Heart and circulatory physiology JO - Am J Physiol Heart Circ Physiol VL - 320 IS - 2 N2 - In sleep apnea, airway obstruction causes intermittent hypoxia (IH). In animal studies, IH-dependent hypertension is associated with loss of vasodilator hydrogen sulfide (H2S), and increased H2S activation of sympathetic nervous system (SNS) activity in the carotid body. We previously reported that inhibiting cystathionine γ-lyase (CSE) to prevent H2S synthesis augments vascular resistance in control rats. The goal of this study was to evaluate the contribution of IH-induced changes in CSE signaling to increased blood pressure and vascular resistance. We hypothesized that chronic IH exposure eliminates CSE regulation of blood pressure (BP) and vascular resistance. In rats instrumented with venous catheters, arterial telemeters, and flow probes on the main mesenteric artery, the CSE inhibitor dl-propargylglycine (PAG, 50 mg/kg/day i.v. for 5 days) increased BP in Sham rats but decreased BP in IH rats [in mmHg, Sham (n = 11): 114 ± 4 to 131 ± 6; IH (n = 8): 131 ± 8 to 115 ± 7 mmHg, P < 0.05]. PAG treatment increased mesenteric vascular resistance in Sham rats but decreased it in IH rats (day 5/day 1: Sham: 1.50 ± 0.07; IH: 0.85 ± 0.19, P < 0.05). Administration of the ganglionic blocker hexamethonium (to evaluate SNS activity) decreased mesenteric resistance in PAG-treated Sham rats more than in saline-treated Sham rats or PAG-treated IH rats. CSE immunoreactivity in IH carotid bodies compared with those from Sham rats. However, CSE staining in small mesenteric arteries was less in arteries from IH than in Sham rats but not different in larger arteries (inner diameter > 200 µm). These results suggest endogenous H2S regulates blood pressure and vascular resistance, but this control is lost after IH exposure with decreased CSE expression in resistance size arteries. IH exposure concurrently increases carotid body CSE expression and relative SNS control of blood pressure, suggesting both vascular and carotid body H2S generation contribute to blood pressure regulation.NEW & NOTEWORTHY These results suggest that CSE's protective role in the vasculature is impaired by simulated sleep apnea, which also upregulates CSE in the carotid body. Thus, this enzyme system can exert both pro- and antihypertensive effects and may contribute to elevated SNS outflow in sleep apnea. SN - 1522-1539 UR - https://www.unboundmedicine.com/medline/citation/33275519/Simulated_sleep_apnea_alters_hydrogen_sulfide_regulation_of_blood_flow_and_pressure_ L2 - https://journals.physiology.org/doi/10.1152/ajpheart.00672.2019?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -