Nitric oxide synthase inhibition with N(G)-monomethyl-l-arginine: Determining the window of effect in the human vasculature.
Nitric Oxide
; 104-105: 51-60, 2020 11 01.
Article
em En
| MEDLINE
| ID: mdl-32979497
ABSTRACT
Nitric oxide synthase (NOS) inhibition with N(G)-monomethyl-l-arginine (L-NMMA) is often used to assess the role of NO in human cardiovascular function. However, the window of effect for L-NMMA on human vascular function is unknown, which is critical for designing and interpreting human-based studies. This study utilized the passive leg movement (PLM) assessment of vascular function, which is predominantly NO-mediated, in 7 young male subjects under control conditions, immediately following intra-arterial L-NMMA infusion (0.24 mgâ
dl-1â
min-1), and at 45-60 and 90-105 min post L-NMMA infusion. The leg blood flow (LBF) and leg vascular conductance (LVC) responses to PLM, measured with Doppler ultrasound and expressed as the change from baseline to peak (ΔLBFpeak and ΔLVCpeak) and area under the curve (LBFAUC and LVCACU), were assessed. PLM-induced robust control ΔLBFpeak (1135 ± 324 mlâ
min-1) and ΔLVCpeak (10.7 ± 3.6 mlâ
min-1â
mmHg-1) responses that were significantly attenuated (704 ± 196 mlâ
min-1 and 6.7 ± 2 mlâ
min-1â
mmHg-1) immediately following L-NMMA infusion. Likewise, control condition PLM ΔLBFAUC (455 ± 202 ml) and ΔLVCAUC (4.0 ± 1.4 mlâ
mmHg-1) were significantly attenuated (141 ± 130 ml and 1.3 ± 1.2 mlâ
mmHg-1) immediately following L-NMMA infusion. However, by 45-60 min post L-NMMA infusion all PLM variables were not significantly different from control, and this was still the case at 90-105 min post L-NMMA infusion. These findings reveal that the potent reduction in NO bioavailability afforded by NOS inhibition with L-NMMA has a window of effect of less than 45-60 min in the human vasculature. These data are particularly important for the commonly employed approach of pharmacologically inhibiting NOS with L-NMMA in the human vasculature.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Óxido Nítrico Sintase
/
ômega-N-Metilarginina
/
Inibidores Enzimáticos
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article