Selective glycolysis blockade in guinea pig pulmonary artery and aorta reverses contractile and electrical responses to acute hypoxia

Soloviev, Anatoly I.; Bondarenko, Alexander I.; Kizub, Igor V.

doi:10.1016/j.vph.2012.06.001

Cited by 3 publications

(3 citation statements)

References 33 publications

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“…A probable explanation of this fact may be a change in the pathway of glucose metabolism in PA of animals with DM under hypoxia influence. It was shown that in healthy animals, selective glycolysis blockade may change this reaction from constriction to dilatation [48]. The transition from oxidative to glycolytic metabolism during hypoxia is provided with HIF-1 due to both inhibiting the conversion of pyruvate to acetyl coenzyme A or lactate [49,50], and increasing efficiency of the electron transfer when switching subunits in cytochrome c oxidase [51].…”

Section: Groupmentioning

confidence: 99%

Influence of type 2 diabetes mellitus on the development of hypoxic pulmonary vasoconstriction

Khromov

Dobrelia

Паршиков

et al. 2020

Фармакологія та лікарська токсикологія

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Hypoxia is currently considered to be an universal factor involved in the development of complications in many diseases including diabetes mellitus (DM). Acute hypoxia causes a systemic reaction with the large circulatory system developing vasodilation and the lesser circulatory system arteries developinghypoxic pulmonary vasoconstriction (HPV), which demonstrates the arteries' ability to regulate pulmonary circulation and maintain normal ventilation-perfusion ratio. Lack of the adequate response to hypoxic effects may be an additional mechanism for the diabetic complications in the cardiovascular system. Despite years of study, the mechanisms of HPV remain largely unclear, as does the effect of diabetes on pulmonary artery reactivity.The aim of the study was to evaluate the effect of high-fat diet and diabetes on the development of the HPV reaction in vivo and in vitro.Studies in rats divided into three groups (control group, a group of rats on a high-fat diet (HFD), and a group of animals with experimental type 2 diabetes mellitus (T2DM)) showed that in rats kept on the high-fat diet, an injection of streptozotocin leads to significant increase in blood glucose levels. In rats kept on the high-fat diet only, this parameter did not differ from the levels in the control animals. In rats kept on HFD and in rats with T2DM model, the right ventricular pressure was significantly higher compared to the control rats.The lung ventilation with a hypoxic gas mixture led to decrease in blood pressure in the systemic circulation in animals of all groups. In the control rats, the pressure in the right ventricular cavity of the heart increased indicating the development of hypoxic pulmonary vasoconstriction. In HFD rats, hypoxic hypoxiahad virtually no effect on the right ventricular pressure. In T2DM rats, an inversion of the hypoxic pulmonary vasoconstriction reaction with decrease in the right ventricular pressure was observed.These results have been confirmed in the in vitro experiments. In lung sections, the responses of the intrapulmonary arteries to hypoxic effects were multi-directional: the pulmonary artery luminal area decreased in the control animals, almost did not change in HFD animals, and increased in T2DM animals.In the rats with experimental diabetes mellitus, the contractile responses of the pulmonary artery ring segments to hypoxia were significantly suppressed compared to the vessels from the control animals.Finding out the exact mechanisms involved in the inversion of the pulmonary vasoconstriction response in diabetes will contribute to a better understanding of the fundamental pathophysiological processes that will promote development of pathogenetically justified approaches to the treatment of this disease and its complications.

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Section: Groupmentioning

confidence: 99%

Influence of type 2 diabetes mellitus on the development of hypoxic pulmonary vasoconstriction

Khromov

Dobrelia

Паршиков

et al. 2020

Фармакологія та лікарська токсикологія

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“…17 We have also reported that inhibition of glycolysis abolishes the hypoxia-induced depolarization of pulmonary artery endothelial cells, 9 suggesting that GJs might be involved in the transduction pathways underlying the glycolysis and endothelium-dependent sustained Phase 2 of HPV.…”

Section: Introductionmentioning

confidence: 96%

“…1,3–6 Intriguingly, both Phase 2 of HPV and the associated Ca 2+ sensitization have a yet unexplained strong dependence on an intact endothelium and glycolysis. 2,4,7–9 …”

Section: Introductionmentioning

confidence: 99%

Gap junctions support the sustained phase of hypoxic pulmonary vasoconstriction by facilitating calcium sensitization

Kizub

Strielkov

Shaifta

et al. 2013

Cardiovascular Research

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AimsTo determine the role of gap junctions (GJs) in hypoxic pulmonary vasoconstriction (HPV).Methods and resultsStudies were performed in rat isolated intrapulmonary arteries (IPAs) mounted on a myograph and in anaesthetized rats. Hypoxia induced a biphasic HPV response in IPAs preconstricted with prostaglandin F2α (PGF2α, 3 µM) or 20 mM K+. The GJ inhibitors 18β-glycyrrhetinic acid (18β-GA, 30 µM), heptanol (3.5 mM), or 2-aminoethoxydiphenyl borate (2-APB) (75 µM) had little effect on the transient Phase 1 of HPV, but abolished the sustained Phase 2 which is associated with Ca2+ sensitization. The voltage-dependent Ca2+ channel blocker diltiazem (10 µM) had no effect on HPV, and did not alter the inhibitory action of 18β-GA. Sustained HPV is enhanced by high glucose (15 mM) via potentiation of Ca2+ sensitization, in the presence of high glucose 18β-GA still abolished sustained HPV. Simultaneous measurement of tension and intracellular Ca2+ using Fura PE-3 demonstrated that whilst 18β-GA abolished tension development during sustained HPV, it did not affect the elevation of intracellular Ca2+. Consistent with this, 18β-GA abolished hypoxia-induced phosphorylation of the Rho kinase target MYPT-1. In anaesthetized rats hypoxia caused a biphasic increase in systolic right ventricular pressure. Treatment with oral 18β-GA (25 mg/kg) abolished the sustained component of the hypoxic pressor response.ConclusionThese results imply that GJs are critically involved in the signalling pathways leading to Rho kinase-dependent Ca2+ sensitization during sustained HPV, but not elevation of intracellular Ca2+, and may explain the dependence of the former on an intact endothelium.

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Hypoxic pulmonary vasoconstriction is lacking in rats with type 1 diabetes

Soloviev

Ivanova

Melnyk

et al. 2019

Clin Exp Pharma Physio

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Hypoxic pulmonary vasoconstriction (HPV) is the most important feature of intact lung circulation that matches local blood perfusion to ventilation. The main goal of this work was to study the effects of diabetes on the development of HPV in rats. The experimental design comprised diabetes mellitus induction by streptozotocin, video‐morphometric measurements of the lumen area of intrapulmonary arteries (iPAs) using perfused lung tissue slices and patch‐clamp techniques. It was shown that iPA lumen size was significantly reduced under physical and chemical hypoxia (7–10 mm Hg) in normal iPA, but, on the contrary, it clearly increased in diabetic lung slices. The amplitude of the outward K+ current in diabetic iPAs smooth muscle cells (SMCs) was two‐fold greater than that seen in healthy cells. Chemical hypoxia led to significant decrease in the amplitude of the K+ outward current in healthy iPA SMCs while it was without effect in diabetic cells. The data obtained clearly indicate a significant dysregulation of vascular tone in pulmonary circulation under diabetes, ie diabetes damages the adaptive mechanism for regulating blood flow from poorly ventilated to better ventilated regions of the lung under hypoxia. This effect could be clinically important for patients with diabetes who have acute or chronic lung diseases associated with the lack of blood oxygenation.

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Selective glycolysis blockade in guinea pig pulmonary artery and aorta reverses contractile and electrical responses to acute hypoxia

Cited by 3 publications

References 33 publications

Influence of type 2 diabetes mellitus on the development of hypoxic pulmonary vasoconstriction

Influence of type 2 diabetes mellitus on the development of hypoxic pulmonary vasoconstriction

Gap junctions support the sustained phase of hypoxic pulmonary vasoconstriction by facilitating calcium sensitization

Hypoxic pulmonary vasoconstriction is lacking in rats with type 1 diabetes

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