Arginase II polymorphisms modify the hypotensive responses to propofol by affecting nitric oxide bioavailability

Autor(es)

Oliveira-Paula, Gustavo H. ^{[1, 2]} ; Coeli-Lacchini, Fernanda Borchers ^[3] ; Ferezin, Leticia Perticarrara ^[4] ; Ferreira, Graziele C. ^[1] ; Pinheiro, Lucas C. ^[5] ; Paula-Garcia, Waynice N. ^[6] ; Garcia, Luis V. ^[6] ; Tanus-Santos, Jose E. ^[1] ; Lacchini, Riccardo ^[5]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto, SP - Brazil

^[2] Albert Einstein Coll Med, Wilf Family Cardiovasc Res Inst, Dept Med, Div Cardiol, New York, NY - USA

^[3] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Analyses Toxicol & Food Sci, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Coll Nursing, Dept Psychiat Nursing & Human Sci, Av Bandeirantes 3900, BR-14040902 Ribeirao Preto, SP - Brazil

^[6] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Orthoped & Anesthesiol, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY; v. 77, n. 6 JAN 2021.
• Citações Web of Science: 0

Resumo

Purpose Propofol anesthesia is usually accompanied by hypotensive responses, which are at least in part mediated by nitric oxide (NO). Arginase I (ARG1) and arginase II (ARG2) compete with NO synthases for their common substrate l-arginine, therefore influencing the NO formation. We examined here whether ARG1 and ARG2 genotypes and haplotypes affect the changes in blood pressure and NO bioavailability in response to propofol. Methods Venous blood samples were collected from 167 patients at baseline and after 10 min of anesthesia with propofol. Genotypes were determined by polymerase chain reaction. Nitrite concentrations were measured by using an ozone-based chemiluminescence assay, while NOx (nitrites + nitrates) levels were determined by using the Griess reaction. Results We found that patients carrying the AG + GG genotypes for the rs3742879 polymorphism in ARG2 gene and the ARG2 GC haplotype show lower increases in nitrite levels and lower decreases in blood pressure after propofol anesthesia. On the other hand, subjects carrying the variant genotypes for the rs10483801 polymorphism in ARG2 gene show more intense decreases in blood pressure (CA genotype) and/or higher increases in nitrite levels (CA and AA genotypes) in response to propofol. Conclusion Our results suggest that ARG2 variants affect the hypotensive responses to propofol, possibly by modifying NO bioavailability. (AU)

• Processo FAPESP: 18/18312-2 - Avaliação dos efeitos epigenéticos da atorvastatina sobre a regulação da expressão de genes relacionados ao óxido nítrico em modelo experimental de hipertensão
• Beneficiário: Riccardo Lacchini
• Linha de fomento: Auxílio à Pesquisa - Regular