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

Abstract:

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. TRIAL REGISTRATION:NCT02442232.

journal_name

Eur J Clin Pharmacol

authors

Oliveira-Paula GH,Coeli-Lacchini FB,Ferezin LP,Ferreira GC,Pinheiro LC,Paula-Garcia WN,Garcia LV,Tanus-Santos JE,Lacchini R

doi

10.1007/s00228-020-03059-9

subject

Has Abstract

pub_date

2021-01-07 00:00:00

eissn

0031-6970

issn

1432-1041

pii

10.1007/s00228-020-03059-9

pub_type

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