Vascular effects of hydrogen sulphide - influence of O2

Erfaida, Yousef (2020) Vascular effects of hydrogen sulphide - influence of O2. PhD thesis, University of Nottingham.

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Hydrogen sulphide (H2S), a toxic gas, has recently been shown to be generated endogenously by biological tissue and it has emerged as a novel and important biological mediator in the vascular system. In blood vessels, H2S has been shown to produce complex actions, including both vasorelaxation and vasoconstriction, through different mechanisms, depending on vessel origin and oxygen levels. This thesis examined the effects of H2S on blood vessels and examined the influence of oxygen concentration on vascular responsiveness and the mechanisms involved. This study also investigated whether H2S contributed to the hypoxic vascular response. Porcine splenic and pulmonary vessels and human chorionic blood vessels were set up in an isometric tension recording system, blood vessels were pre-contracted and responses to the H2S donor, NaHS, were produced in the presence and absence inhibitors, under 95% O2:5% CO2, 95% Air: 5% CO2 and 95% N2:5% CO2 gassing conditions. Western blot analysis was carried out to determine Cystathionine β synthase (CBS) and Cystathionine γ lyase (CSE) expression in porcine splenic and pulmonary arteries.

Changing oxygen concentrations altered the nature of the response observed with NaHS. Generally, in both porcine splenic arteries (PSA) and porcine pulmonary veins (PPV), gassing with physiological levels of O2 (95% air: 5% CO2), was associated with NaHS causing a contractile response, while, gassing with sub-physiological levels (95% N2: 5% CO2), NaHS caused a relaxant response in PSA. The nitric oxide (NO) synthase inhibitor L-NAME, significantly abolished contractile response in PSA, indicating an interaction with NO. In porcine splenic veins (PSV) and porcine pulmonary arteries (PPA) under physiological gassing condition (95% N2: 5% CO2), NaHS-induced vasorelaxation was observed. The vasorelaxatory responses were abolished by L-NAME, showing that NaHS is activating NOS to generate NO and cause vasorelaxation. In human chorionic blood vessels, NaHS caused vasoconstriction under physiological gassing condition (95% N2: 5% CO2). L-NAME was without effect on the contraction, and so NO is not involved in this human blood vessel.

Both CBS and CSE are expressed in porcine splenic and pulmonary arteries. L-cysteine induced a contractile response in PSA and PPA but this was not blocked by the H2S synthesis- enzymes inhibitors, indicating that L-cysteine-elicited contraction was not through a H2S-dependent mechanism. Hypoxia caused a biphasic response in the PSA; a transient contraction followed by prolonged relaxation. The relaxation response was attenuated by AOAA, suggesting that H2S participates in vascular responses to hypoxia with CBS the likely source of H2S production. Hypoxia-induced vasoconstriction was observed in both PSA and PPA. The vasocontractile responses were abolished by L-NAME, showing that hypoxia decreases the sustained release of NO from the vascular endothelium.

In summary, these data show that O2 influenced H2S responses. At more physiological levels of O2 the predominant response is vasoconstriction, often mediated by H2S ‘mopping up’ endogenous NO. The predominant response in PSV and PPA was vasorelaxation, evoked by activating NOS to generate NO. Responses to hypoxia, in part, involve endogenous H2S generation, suggesting that H2S can act as an oxygen sensor in PSA.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Dunn, William
Leach, Lopa
Keywords: Blood vessels; Oxygen concentration; Vascular responsiveness; Hydrogen sulphide
Subjects: Q Science > QL Zoology > QL801 Anatomy
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Life Sciences
Item ID: 59593
Depositing User: Erfaida, Yousef
Date Deposited: 25 Jun 2020 08:16
Last Modified: 25 Jun 2020 08:16

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