Inhalational Anesthetics Up-Regulate Constitutive and Lipopolysaccharide-Induced Inducible Nitric Oxide Synthase Expression and Activity
- Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville, VA 22906-0010
Abstract
Nitric oxide (NO) is an important biological messenger involved in the regulation of blood vessel tone, neurotransmission, inflammatory responses, and host defenses. Inhalational anesthetics have been shown to inhibit the function of the NO signaling pathway in a variety of tissues. In addition, acute inhibition of the NO signaling pathway significantly reduced the required alveolar concentration of halothane or isoflurane for anesthesia, which suggests a role for the NO signaling pathway in mechanisms of anesthesia and consciousness. We now report that inhalational anesthetics affect gene expression of nitric oxide synthases (NOS) (EC 1.14.13.39), the enzymes that synthesize NO from l-arginine. Both halothane and isoflurane, at clinically relevant concentrations, significantly up-regulate the mRNA, protein, and activity level of NOS in lipopolysaccharide-treated macrophages (inducible NOS; type II NOS), and bovine pulmonary endothelial cells (endothelial constitutive NOS; type III NOS). This is a novel interaction between inhalational anesthetics and the NO signaling pathway and has wide-ranging implications for both clinical medicine and experimental biology.
Footnotes
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Send reprint requests to: Dr. Roger A. Johns, Department of Anesthesiology, P.O. Box 10010, University of Virginia Health Sciences Center, Charlottesville, VA 22906-0010. E-mail: raj2d{at}virginia.edu
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This study was supported by National Institutes of Health Grants R01-GM49111, and R01-HL39706
- Abbreviations:
- NO
- nitric oxide
- NOS
- nitric oxide synthase
- BPAEC
- bovine pulmonary artery endothelial cells
- eNOS
- endothelial constitutive nitric oxide synthase
- iNOS
- inducible nitric oxide synthase
- l-NAME
- nitroG-l-arginine-methyl-ester
- LPS
- lipopolysaccharide
- PKC
- protein kinase C
- EGTA
- ethylene glycol bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid
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- Received December 20, 1996.
- Accepted June 20, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
