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Assessment of Vascular Tone Responsiveness using Isolated Mesenteric Arteries with a Focus on Modulation by Perivascular Adipose Tissues
Published on: June 3, 2019
Changes in extracellular pH mediate the chronotropic responses to L-arginine
P Musialek1, D J Paterson, B Casadei
1Department of Cardiovascular Medicine, John Radcliffe Hospital, Oxford, UK. piotr.musialek@clinical-medicine.ox.ac.uk
Cardiovascular Research
|February 26, 2000
Summary
L-arginine (L-Arg) affects heart rate (HR) through a pH-mediated mechanism, not nitric oxide (NO). Different L-Arg formulations can alter pH, confounding HR effect assessments.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
Background:
- Exogenous nitric oxide (NO) stimulates the hyperpolarization-activated current (I(f)) to increase heart rate (HR).
- Investigating L-arginine (L-Arg) as a potential modulator of endogenous NO production and its chronotropic effects is crucial.
Purpose of the Study:
- To determine if L-arginine (L-Arg) can mimic the chronotropic effect of nitric oxide (NO) by enhancing endogenous NO production.
- To evaluate the impact of different L-Arg formulations (free base vs. hydrochloride) on heart rate (HR).
Main Methods:
- Spontaneously beating guinea pig atria were used to assess heart rate (HR) responses to varying L-Arg concentrations.
- Comparisons were made with D-arginine (D-Arg) and L-lysine (L-Lys) in both free base (FB) and hydrochloride (HCl) formulations.
- Perfusate pH changes and nitric oxide (NO) scavenging were monitored to isolate the mechanism of HR alteration.
Main Results:
- L-arginine free base (L-ArgFB) at concentrations above 100 µmol/l caused a reversible, dose-dependent increase in HR.
- D-arginine free base (D-ArgFB) and L-lysine free base (L-LysFB) produced similar HR increases, correlating with increased perfusate pH.
- L-arginine hydrochloride (L-ArgHCl) and other HCl formulations significantly decreased HR and perfusate pH, indicating a pH-dependent effect independent of NO.
Conclusions:
- In vitro, L-arginine (L-Arg) significantly influences heart rate (HR) via a pH-mediated pathway, independent of nitric oxide (NO).
- The formulation of L-Arg (free base vs. hydrochloride) critically affects perfusate pH, which can confound the assessment of its biological effects.
- These findings highlight the importance of controlling pH when evaluating the pharmacological actions of amino acids like L-Arg.
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