Expression of Inducible Nitric Oxide Synthase Depresses β-Adrenergic–Stimulated Calcium Release From the Sarcoplasmic Reticulum in Intact Ventricular Myocytes
Why the study?
Does iNOS expression alter the function of the sarcoplasmic reticulum Ca2+ release channel during beta-adrenergic stimulation in ventricular myocytes?
Population
Rat ventricular myocytes isolated 6 hours after lipopolysaccharide injection to induce iNOS expression, and…
Comparison
Adenylate cyclase activator forskolin with or… vs Normal myocytes (iNOS not expressed)
Design
Preclinical
Authors
Discussion
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Implication
May explain beta-adrenergic hyporesponsiveness in heart failure; hypothesis-generating for iNOS-targeted therapies.
Structured PICO
Does iNOS expression alter the function of the sarcoplasmic reticulum Ca2+ release channel during beta-adrenergic stimulation in ventricular myocytes?
P
Population
Rat ventricular myocytes isolated 6 hours after lipopolysaccharide (LPS) injection (10 mg/kg) to induce iNOS expression, and myocytes isolated from a failing human heart.
I
Intervention
Adenylate cyclase activator forskolin (100 nmol/L) with or without iNOS inhibitor aminoguanidine (1 mmol/L) or guanylate cyclase inhibitor ODQ (10 micromol/L)
C
Comparator
Normal myocytes (iNOS not expressed)
O
Outcome
Ca2+ spark frequency (CaSpF) and twitch Ca2+ transient amplitude measured by confocal microscopysurrogate
iNOS/NO depresses beta-adrenergic-stimulated RyR function through a cGMP-independent pathway, which may explain beta-adrenergic hyporesponsiveness in cardiomyopathies and heart failure.
Cite This Study
Ziolo et al. (2001) studied this question.