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Arginase II polymorphisms modify the hypotensive responses to propofol by affecting nitric oxide bioavailability
Gustavo H Oliveira-Paula1,2, Fernanda Borchers Coeli-Lacchini3, Letícia Perticarrara Ferezin4
1Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
European Journal of Clinical Pharmacology
|January 7, 2021
Summary
Genetic variations in the ARG2 gene influence blood pressure changes and nitric oxide (NO) levels during propofol anesthesia. Certain ARG2 genotypes are linked to reduced hypotensive responses and altered NO bioavailability.
Area of Science:
- Pharmacogenomics
- Anesthesiology
- Cardiovascular Physiology
Background:
- Propofol anesthesia commonly causes hypotension, partly mediated by nitric oxide (NO).
- Arginase enzymes (ARG1 and ARG2) compete with NO synthases for L-arginine, impacting NO production.
- Genetic variations in arginase genes may influence patient responses to propofol.
Purpose of the Study:
- To investigate whether ARG1 and ARG2 genotypes and haplotypes affect blood pressure and NO bioavailability changes during propofol anesthesia.
- To explore the role of arginase genetic variants in propofol-induced hypotension.
Main Methods:
- Collected venous blood samples from 167 patients undergoing propofol anesthesia.
- Determined ARG1 and ARG2 genotypes using polymerase chain reaction.
- Measured nitrite and NOx (nitrite + nitrate) levels using chemiluminescence and Griess reaction assays, respectively.
Main Results:
- Patients with specific ARG2 polymorphisms (rs3742879 AG+GG genotypes, ARG2 GC haplotype) exhibited smaller increases in nitrite and less pronounced blood pressure drops post-propofol.
- Carriers of variant genotypes for the ARG2 rs10483801 polymorphism showed greater blood pressure decreases (CA genotype) and/or higher nitrite level increases (CA, AA genotypes).
Conclusions:
- Genetic variants in the ARG2 gene appear to modulate hypotensive responses to propofol anesthesia.
- These ARG2 variants may influence NO bioavailability, thereby affecting blood pressure regulation during anesthesia.
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