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The Potential Role of Hydrogen Sulfide in the Regulation of Cerebrovascular Tone.

ABSTRACT: A better understanding of the regulation of cerebrovascular circulation is of great importance because stroke and other cerebrovascular diseases represent a major concern in healthcare leading to millions of deaths yearly. The circulation of the central nervous system is regulated in a highly complex manner involving many local factors and hydrogen sulfide (H₂S) is emerging as one such possible factor. Several lines of evidence support that H₂S takes part in the regulation of vascular tone. Examinations using either exogenous treatment with H₂S donor molecules or alterations to the enzymes that are endogenously producing this molecule revealed numerous important findings about its physiological and pathophysiological role. The great majority of these studies were performed on vessel segments derived from the systemic circulation but there are important observations made using cerebral vessels as well. The findings of these experimental works indicate that H₂S is having a complex, pleiotropic effect on the vascular wall not only in the systemic circulation but in the cerebrovascular region as well. In this review, we summarize the most important experimental findings related to the potential role of H₂S in the cerebral circulation.

SUBMITTER: Dongo E

PROVIDER: S-EPMC7766080 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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The Potential Role of Hydrogen Sulfide in the Regulation of Cerebrovascular Tone.

Dongó Eleni E Kiss Levente L

Biomolecules 20201216 12

A better understanding of the regulation of cerebrovascular circulation is of great importance because stroke and other cerebrovascular diseases represent a major concern in healthcare leading to millions of deaths yearly. The circulation of the central nervous system is regulated in a highly complex manner involving many local factors and hydrogen sulfide (H<sub>2</sub>S) is emerging as one such possible factor. Several lines of evidence support that H<sub>2</sub>S takes part in the regulation ...[more]

PMID: 33339440

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Project description:Hydrogen sulfide (H2S) dilates isolated arteries, and knockout of the H2S-synthesizing enzyme cystathionine γ-lyase (CSE) increases blood pressure. However, the contributions of endogenously produced H2S to blood flow regulation in specific vascular beds are unknown. Published studies in isolated arteries show that CSE production of H2S influences vascular tone more in small mesenteric arteries than in renal arteries or the aorta. Therefore, the goal of this study was to evaluate H2S regulation of blood pressure, vascular resistance, and regional blood flows using chronically instrumented rats. We hypothesized that during whole animal CSE inhibition, vascular resistance would increase more in the mesenteric than the renal circulation. Under anesthesia, CSE inhibition [β-cyanoalanine (BCA), 30 mg/kg bolus + 5 mg·kg-1·min-1 for 20 min iv) rapidly increased mean arterial pressure (MAP) more than saline administration (%Δ: saline -1.4 ± 0.75 vs. BCA 7.1 ± 1.69, P < 0.05) but did not change resistance (MAP/flow) in either the mesenteric or renal circulation. In conscious rats, BCA infusion similarly increased MAP (%Δ: saline -0.8 ± 1.18 vs. BCA 8.2 ± 2.6, P < 0.05, n = 7) and significantly increased mesenteric resistance (saline 0.9 ± 3.1 vs. BCA 15.6 ± 6.5, P < 0.05, n = 12). The H2S donor Na2S (50 mg/kg) decreased blood pressure and mesenteric resistance ,but the fall in resistance was not significant. Inhibiting CSE for multiple days with dl-proparglycine (PAG, 50 mg·kg-1·min-1 iv bolus for 5 days) significantly increased vascular resistance in both mesenteric (ratio of day 1: saline 0.86 ± 0.033 vs. PAG 1.79 ± 0.38) and renal circulations (ratio of day 1: saline 1.26 ± 0.22 vs. 1.98 ± 0.14 PAG). These results support our hypothesis that CSE-derived H2S is an important regulator of blood pressure and vascular resistance in both mesenteric and renal circulations. Furthermore, inhalation anesthesia diminishes the effect of CSE inhibition on vascular tone.NEW & NOTEWORTHY These results suggest that CSE-derived H2S has a prominent role in regulating blood pressure and blood flow under physiological conditions, which may have been underestimated in prior studies in anesthetized subjects. Therefore, enhancing substrate availability or enzyme activity or dosing with H2S donors could be a novel therapeutic approach to treat cardiovascular diseases.

Dataset Information

The Potential Role of Hydrogen Sulfide in the Regulation of Cerebrovascular Tone.

Publications

The Potential Role of Hydrogen Sulfide in the Regulation of Cerebrovascular Tone.

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