S-nitroso-L-cysteine stereoselectively blunts the adverse effects of morphine on breathing and arterial blood gas chemistry while promoting analgesia

dc.contributor.authorGetsy, Paulina M.
dc.contributor.authorYoung, Alex P.
dc.contributor.authorBates, James N.
dc.contributor.authorBaby, Santhosh M.
dc.contributor.authorSeckler, James M.
dc.contributor.authorGrossfield, Alan
dc.contributor.authorHsieh, Yee-Hsee
dc.contributor.authorLewis, Tristan H.J.
dc.contributor.authorJenkins, Michael W.
dc.contributor.authorGaston, Benjamin
dc.contributor.authorLewis, Stephen J.
dc.contributor.departmentPediatrics, School of Medicine
dc.date.accessioned2023-08-25T12:05:39Z
dc.date.available2023-08-25T12:05:39Z
dc.date.issued2022
dc.description.abstractS-nitrosothiols exert multiple effects on neural processes in the central and peripheral nervous system. This study shows that intravenous infusion of S-nitroso-L-cysteine (SNO-L-CYS, 1 μmol/kg/min) in anesthetized male Sprague Dawley rats elicits (a) sustained increases in minute ventilation, via increases in frequency of breathing and tidal volume, (b) a decrease in Alveolar-arterial (A-a) gradient, thus improving alveolar gas-exchange, (c) concomitant changes in arterial blood-gas chemistry, such as an increase in pO2 and a decrease in pCO2, (d) a decrease in mean arterial blood pressure (MAP), and (e) an increase in tail-flick (TF) latency (antinociception). Infusion of S-nitroso-D-cysteine (SNO-D-CYS, 1 μmol/kg/min, IV), did not elicit similar responses, except for a sustained decrease in MAP equivalent to that elicited by SNO-L-CYS. A bolus injection of morphine (2 mg/kg, IV) in rats receiving an infusion of vehicle elicited (a) sustained decreases in frequency of breathing tidal volume, and therefore minute ventilation, (b) a sustained decrease in MAP, (c) sustained decreases in pH, pO2 and maximal sO2 with sustained increases in pCO2 and A-a gradient, and (d) a sustained increase in TF latency. In rats receiving SNO-L-CYS infusion, morphine elicited markedly smaller changes in minute ventilation, arterial blood gas chemistry, A-a gradient and MAP. In contrast, the antinociceptive effects of morphine were enhanced in rats receiving the infusion of SNO-L-CYS. The morphine-induced responses in rats receiving SNO-D-CYS infusion were similar to vehicle-infused rats. These data are the first to demonstrate that infusion of an S-nitrosothiol, such as SNO-L-CYS, can stereoselectively ameliorate the adverse effects of morphine on breathing and alveolar gas exchange while promoting antinociception.
dc.eprint.versionAuthor's manuscript
dc.identifier.citationGetsy PM, Young AP, Bates JN, et al. S-nitroso-L-cysteine stereoselectively blunts the adverse effects of morphine on breathing and arterial blood gas chemistry while promoting analgesia. Biomed Pharmacother. 2022;153:113436. doi:10.1016/j.biopha.2022.113436
dc.identifier.urihttps://hdl.handle.net/1805/35126
dc.language.isoen_US
dc.publisherElsevier
dc.relation.isversionof10.1016/j.biopha.2022.113436
dc.relation.journalBiomedicine & Pharmacotherapy
dc.rightsPublisher Policy
dc.sourcePMC
dc.subjectAntinociception
dc.subjectMorphine
dc.subjectRespiratory depression
dc.subjectS-nitrosothiol
dc.subjectSprague Dawley rats
dc.titleS-nitroso-L-cysteine stereoselectively blunts the adverse effects of morphine on breathing and arterial blood gas chemistry while promoting analgesia
dc.typeArticle
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