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Adaptive Mechanisms of Baroreflectory Regulation of the Cardiovascular System in Extreme Hyperoxia

  • Comparative and Ontogenic Biochemistry
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Abstract

The cardiovascular system of vertebrates, including humans, is well known to respond to hyperoxia by vasoconstriction, bradycardia and decreased contractility of the left heart ventricle. We hypothesized that all of these responses are components of the baroreflex that regulates blood pressure and circulation in hyperoxia. To test this hypothesis, we carried out experiments on awake rats in which the dynamics of arterial blood pressure, organ blood flow (brain, kidney, lower limbs) and ECG was tracked in response to oxygen breathing at 1, 3 and 5 ATA. The afferent and efferent baroreflex pathways were studied using denervation of the carotid baroreceptors and transection of the aortic depressor nerves and vagus nerve. The baroreflex effectiveness was assessed using phenylephrine injections or spontaneous changes in blood pressure. To activate the GABAergic system, nipecotic acid was injected into the lateral ventricle of the brain. Our studies demonstrated the presence of all the baroreflex components in hyperoxia which were triggered by a sharp rise in blood pressure due to systemic vasoconstriction. Hyperoxic vasoconstriction, in turn, arose due to endothelium-derived nitric oxide (NO) which binds to superoxide anions followed by a loss of the vasodilator component of vascular tone. Aortic and carotid sinus baroreceptors with ascending nerve fibers were identified as an afferent component of the hyperoxic baroreflex. Bradycardia and a decrease in cardiac output, resulting from baroreflex activation by hyperoxia, are actualized via efferent sympathetic and parasympathetic pathways. At 1 and 3 ATA the baroreflex effectiveness increased compared to atmospheric air breathing, but extreme hyperoxia (5 ATA) suppressed the baroreflex mechanism. Activation of the GABAergic system in the cerebral cortex by nipecotic acid prevented the loss of the hyperoxic baroreflex. In hyperoxia, the baroreflex mechanism realizes adaptive responses of the cardiovascular system aimed at restraining the delivery of excess oxygen to an organism and mitigates activation of the sympathetic nervous system.

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Funding

This work was supported by the Program of fundamental studies of the Presidium of the Russian Academy of Sciences no. 18 “Biomedical technologies: innovative developments” (project no. 0132-2018-0011), Russian Foundation for Basic Research (grant no. 15-04-05970), and, in part, within the state assignment to Sechenov Institute of Evolutionary Physiology and Biochemistry, RAS (no. 007-00096-18, reg. no. AAAA-A18-118012290142-9).

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Correspondence to O. S. Alekseeva.

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All applicable international, national and institutional principles of handling and using experimental animals for scientific purposes were observed. This study did not involve human subjects as research objects.

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Russian Text © The Author(s), 2019, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2019, Vol. 55, No. 5, pp. 316–323.

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Zhilyaev, S.Y., Platonova, T.F., Alekseeva, O.S. et al. Adaptive Mechanisms of Baroreflectory Regulation of the Cardiovascular System in Extreme Hyperoxia. J Evol Biochem Phys 55, 365–371 (2019). https://doi.org/10.1134/S002209301905003X

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