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      Opposing responses of the rat pulmonary artery and vein to phenylephrine and other agents in vitro

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          Abstract

          Background

          Different from current cognition, our study demonstrated that adrenergic receptors agonist phenylephrine significantly relaxed isolated pulmonary artery but constricted pulmonary veins. Through comparing differences in the effects of commonly used vasoactive drugs on pulmonary artery and veins, the study aimed to improve efficiency and accuracy of isolated pulmonary vascular experiments, and to provide experimental basis for clinical drug use.

          Methods

          The contractile responses of pulmonary arteries and veins from twelve-week-old Male Sprague-Dawley rats to phenylephrine, arginine vasopressin (AVP), U46619, endothelin-1, and potassium chloride (KCl) were recorded, as well as the relaxation in response to phenylephrine, AVP, acetylcholine. To further explore the mechanism, some vessels was also pre-incubated with adrenergic receptors antagonists propranolol, prazosin and nitric oxide synthesis inhibitor N[gamma]-nitro-L-arginine methyl ester (L-NAME) before addition of the experimental drugs.

          Results

          Phenylephrine constricted pulmonary veins directly, but constricted pulmonary artery only after incubation with propranolol or/and L-NAME. The pulmonary artery exhibited significant relaxation to AVP with or without L-NAME incubation. AVP more clearly constricted the veins after incubation with L-NAME. Changes in vascular tension also varied from pulmonary artery to veins for KCl stimulation. Different from phenomena presented in veins, acetylcholine did not relax pulmonary artery preconstricted by KCl, U46619, and endothelin-1.

          Conclusions

          According to the results, phenylephrine, KCl, AVP, and acetylcholine could be used to distinguish pulmonary arteries and pulmonary veins in vitro. This also suggested that the pulmonary arteries and pulmonary veins have great differences in physiology and drug reactivity.

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          Most cited references26

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          EDHF: bringing the concepts together

          Endothelial cells synthesize and release vasoactive mediators in response to various neurohumoural substances (e.g. bradykinin or acetylcholine) and physical stimuli (e.g. cyclic stretch or fluid shear stress). The best-characterized endothelium-derived relaxing factors are nitric oxide and prostacyclin. However, an additional relaxant pathway associated with smooth muscle hyperpolarization also exists. This hyperpolarization was originally attributed to the release of an endothelium-derived hyperpolarizing factor (EDHF) that diffuses to and activates smooth muscle K(+) channels. More recent evidence suggests that endothelial cell receptor activation by these neurohumoural substances opens endothelial cell K(+) channels. Several mechanisms have been proposed to link this pivotal step to the subsequent smooth muscle hyperpolarization. The main concepts are considered in detail in this review.
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            EDHF: spreading the influence of the endothelium.

            Our view of the endothelium was transformed around 30 years ago, from one of an inert barrier to that of a key endocrine organ central to cardiovascular function. This dramatic change followed the discoveries that endothelial cells (ECs) elaborate the vasodilators prostacyclin and nitric oxide. The key to these discoveries was the use of the quintessentially pharmacological technique of bioassay. Bioassay also revealed endothelium-derived hyperpolarizing factor (EDHF), particularly important in small arteries and influencing blood pressure and flow distribution. The basic idea of EDHF as a diffusible factor causing smooth muscle hyperpolarization (and thus vasodilatation) has evolved into one of a complex pathway activated by endothelial Ca(2+) opening two Ca(2+) -sensitive K(+) -channels, K(Ca)2.3 and K(Ca)3.1. Combined application of apamin and charybdotoxin blocked EDHF responses, revealing the critical role of these channels as iberiotoxin was unable to substitute for charybdotoxin. We showed these channels are arranged in endothelial microdomains, particularly within projections towards the adjacent smooth muscle, and close to interendothelial gap junctions. Activation of K(Ca) channels hyperpolarizes ECs, and K(+) efflux through them can act as a diffusible 'EDHF' stimulating Na(+) /K(+) -ATPase and inwardly rectifying K-channels. In parallel, hyperpolarizing current can spread from the endothelium to the smooth muscle through myoendothelial gap junctions upon endothelial projections. The resulting radial hyperpolarization mobilized by EDHF is complemented by spread of hyperpolarization along arteries and arterioles, effecting distant dilatation dependent on the endothelium. So the complexity of the endothelium still continues to amaze and, as knowledge evolves, provides considerable potential for novel approaches to modulate blood pressure. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
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              Vasoregulation by the beta1 subunit of the calcium-activated potassium channel.

              Small arteries exhibit tone, a partially contracted state that is an important determinant of blood pressure. In arterial smooth muscle cells, intracellular calcium paradoxically controls both contraction and relaxation. The mechanisms by which calcium can differentially regulate diverse physiological responses within a single cell remain unresolved. Calcium-dependent relaxation is mediated by local calcium release from the sarcoplasmic reticulum. These 'calcium sparks' activate calcium-dependent potassium (BK) channels comprised of alpha and beta1 subunits. Here we show that targeted deletion of the gene for the beta1 subunit leads to a decrease in the calcium sensitivity of BK channels, a reduction in functional coupling of calcium sparks to BK channel activation, and increases in arterial tone and blood pressure. The beta1 subunit of the BK channel, by tuning the channel's calcium sensitivity, is a key molecular component in translating calcium signals to the central physiological function of vasoregulation.
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                Author and article information

                Contributors
                lizhou@shmu.edu.cn
                drhuangsq@163.com
                Journal
                BMC Pulm Med
                BMC Pulm Med
                BMC Pulmonary Medicine
                BioMed Central (London )
                1471-2466
                5 June 2021
                5 June 2021
                2021
                : 21
                : 189
                Affiliations
                [1 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Department of Anaesthesia, Obstetrics and Gynecology Hospital, , Fudan University, ; 128 Shenyang road, Shanghai, 200090 China
                [2 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Department of Physiology and Pathophysiology, School of Basic Medicine Science, , Fudan University, ; 130 Dongan Road, Shanghai, 200032 China
                [3 ]GRID grid.410737.6, ISNI 0000 0000 8653 1072, Department of Anesthesiology and Perioperative Medicine, Guangzhou Women and Children’s Medical Center, , Guangzhou Medical University, ; 9# Jinsui Road, Guangzhou, 510623 China
                Article
                1558
                10.1186/s12890-021-01558-8
                8180060
                34090386
                4ba9749e-8165-42c6-ae10-fb8cc6891c46
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 1 July 2020
                : 27 May 2021
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2021

                Respiratory medicine
                arginine vasopressin,phenylephrine,potassium chloride,pulmonary artery,pulmonary vein,vascular tension

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