PMID- 30760775 OWN - NLM STAT- MEDLINE DCOM- 20200825 LR - 20200825 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 9 IP - 1 DP - 2019 Feb 13 TI - Argon reduces the pulmonary vascular tone in rats and humans by GABA-receptor activation. PG - 1902 LID - 10.1038/s41598-018-38267-y [doi] LID - 1902 AB - Argon exerts neuroprotection. Thus, it might improve patients' neurological outcome after cerebral disorders or cardiopulmonary resuscitation. However, limited data are available concerning its effect on pulmonary vessel and airways. We used rat isolated perfused lungs (IPL) and precision-cut lung slices (PCLS) of rats and humans to assess this topic. IPL: Airway and perfusion parameters, oedema formation and the pulmonary capillary pressure (P(cap)) were measured and the precapillary and postcapillary resistance (R(post)) was calculated. In IPLs and PCLS, the pulmonary vessel tone was enhanced with ET-1 or remained unchanged. IPLs were ventilated and PCLS were gassed with argon-mixture or room-air. IPL: Argon reduced the ET-1-induced increase of P(cap), R(post) and oedema formation (p < 0.05). PCLS (rat): Argon relaxed naive pulmonary arteries (PAs) (p < 0.05). PCLS (rat/human): Argon attenuated the ET-1-induced contraction in PAs (p < 0.05). Inhibition of GABA(B)-receptors abolished argon-induced relaxation (p < 0.05) in naive or ET-1-pre-contracted PAs; whereas inhibition of GABA(A)-receptors only affected ET-1-pre-contracted PAs (p < 0.01). GABA(A/B)-receptor agonists attenuated ET-1-induced contraction in PAs and baclofen (GABA(B)-agonist) even in pulmonary veins (p < 0.001). PLCS (rat): Argon did not affect the airways. Finally, argon decreases the pulmonary vessel tone by activation of GABA-receptors. Hence, argon might be applicable in patients with pulmonary hypertension and right ventricular failure. FAU - Suleiman, Said AU - Suleiman S AD - Institute of Pharmacology and Toxicology, Medical Faculty RWTH-Aachen, 52074, Aachen, Germany. FAU - Klassen, Sergej AU - Klassen S AD - Institute of Pharmacology and Toxicology, Medical Faculty RWTH-Aachen, 52074, Aachen, Germany. FAU - Katz, Ira AU - Katz I AD - Medical Research & Development, Air Liquide Sante Internationale, Centre de Recherche Paris-Saclay, 78354, Jouy-en-Josas, France. FAU - Balakirski, Galina AU - Balakirski G AD - Institute of Pharmacology and Toxicology, Medical Faculty RWTH-Aachen, 52074, Aachen, Germany. FAU - Krabbe, Julia AU - Krabbe J AUID- ORCID: 0000-0003-4205-9783 AD - Institute of Pharmacology and Toxicology, Medical Faculty RWTH-Aachen, 52074, Aachen, Germany. FAU - von Stillfried, Saskia AU - von Stillfried S AD - Institute of Pathology, Medical Faculty RWTH Aachen, 52074, Aachen, Germany. FAU - Kintsler, Svetlana AU - Kintsler S AD - Institute of Pathology, Medical Faculty RWTH Aachen, 52074, Aachen, Germany. FAU - Braunschweig, Till AU - Braunschweig T AD - Institute of Pathology, Medical Faculty RWTH Aachen, 52074, Aachen, Germany. FAU - Babendreyer, Aaron AU - Babendreyer A AD - Institute of Pharmacology and Toxicology, Medical Faculty RWTH-Aachen, 52074, Aachen, Germany. FAU - Spillner, Jan AU - Spillner J AD - Department of Cardiac and Thoracic Surgery, Medical Faculty RWTH Aachen, 52074, Aachen, Germany. FAU - Kalverkamp, Sebastian AU - Kalverkamp S AD - Department of Cardiac and Thoracic Surgery, Medical Faculty RWTH Aachen, 52074, Aachen, Germany. FAU - Schroder, Thomas AU - Schroder T AD - Department of Surgery, Luisenhospital Aachen, 52064, Aachen, Germany. FAU - Moeller, Manfred AU - Moeller M AD - Institute for Occupational, Social and Environmental Medicine, Medical Faculty RWTH Aachen, 52074, Aachen, Germany. FAU - Coburn, Mark AU - Coburn M AD - Department of Anaesthesiology, Medical Faculty RWTH Aachen, 52074, Aachen, Germany. FAU - Uhlig, Stefan AU - Uhlig S AD - Institute of Pharmacology and Toxicology, Medical Faculty RWTH-Aachen, 52074, Aachen, Germany. FAU - Martin, Christian AU - Martin C AD - Institute of Pharmacology and Toxicology, Medical Faculty RWTH-Aachen, 52074, Aachen, Germany. FAU - Rieg, Annette D AU - Rieg AD AUID- ORCID: 0000-0002-7043-5494 AD - Department of Anaesthesiology, Medical Faculty RWTH Aachen, 52074, Aachen, Germany. arieg@ukaachen.de. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190213 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Endothelin-1) RN - 0 (GABA-B Receptor Agonists) RN - 0 (Receptors, GABA-B) RN - 67XQY1V3KH (Argon) RN - H789N3FKE8 (Baclofen) SB - IM MH - Animals MH - Argon/*pharmacology MH - Baclofen/pharmacology MH - Blood Pressure/drug effects MH - Edema/chemically induced/prevention & control MH - Endothelin-1/pharmacology MH - Female MH - GABA-B Receptor Agonists/pharmacology MH - Hemodynamics/drug effects MH - Humans MH - Lung/pathology/physiology MH - Muscle Contraction/drug effects MH - Pulmonary Artery/*drug effects/physiology MH - Rats MH - Rats, Wistar MH - Receptors, GABA-B/chemistry/*metabolism PMC - PMC6374423 COIS- Said Suleiman has no financial and non-financial interests. Sergej Klassen has no financial and non-financial interests. Ira Katz works for Air Liquide. Even he could have a commercial interest; he did not influence the design or the outcome of the study. Ira Katz was very helpful with his experience in view of physiochemical properties of laboratory gases to explain and interpret some unexpected effects of argon on the airway parameters. Galina Balakirski has no financial and non-financial interests. Julia Krabbe has no financial and non-financial interests. Saskia von Stillfried has no financial and non-financial interests. Svetlana Kintsler has no financial and non-financial interests. Till Braunschweig has no financial and non-financial interests. Aaron Babendreyer has no financial and non-financial interests. Jan Spillner has no financial and non-financial interests. Sebastian Kalverkamp has no financial and non-financial interests. Thomas Schroder has no financial and non-financial interests. Manfred Moeller has no financial and non-financial interests. Mark Coburn has no financial and non-financial interests. Stefan Uhlig has no financial and non-financial interests. Christian Martin has no financial and non-financial interests. Annette D Rieg has no financial and non-financial interests. EDAT- 2019/02/15 06:00 MHDA- 2020/08/26 06:00 PMCR- 2019/02/13 CRDT- 2019/02/15 06:00 PHST- 2018/09/12 00:00 [received] PHST- 2018/12/21 00:00 [accepted] PHST- 2019/02/15 06:00 [entrez] PHST- 2019/02/15 06:00 [pubmed] PHST- 2020/08/26 06:00 [medline] PHST- 2019/02/13 00:00 [pmc-release] AID - 10.1038/s41598-018-38267-y [pii] AID - 38267 [pii] AID - 10.1038/s41598-018-38267-y [doi] PST - epublish SO - Sci Rep. 2019 Feb 13;9(1):1902. doi: 10.1038/s41598-018-38267-y.