Key Points
- To investigate whether nitric oxide modulates cardiac function in isolated atria and ventricular cardiomyocytes during isoproterenol-induced heart failure.
- Administered isoproterenol (5 mg/kg/day, intraperitoneally) or vehicle to rats for 1 week to induce heart failure.
- Assessed left ventricular hemodynamics via catheterization, along with chronotropy in isolated atria and contractility in paced left ventricular myocytes with and without the NOS inhibitor L-NAME.
- Quantified left ventricular protein expression of nitric oxide synthases (eNOS, iNOS, nNOS) and allosteric modulators (hsp90, caveolin-1, caveolin-3).
- Isoproterenol treatment increased left ventricular mass by 33% and significantly decreased systolic (dp/dtmax) and diastolic (dp/dtmin) function (both P < 0.05).
- Isolated atria from failing hearts demonstrated a lower spontaneous beating rate (P < 0.05), which increased with L-NAME, while L-NAME reduced contractility in control myocytes but not failing myocytes.
- Protein expression of eNOS, iNOS, and hsp90 significantly increased in failing left ventricles, whereas nNOS, caveolin-1, and caveolin-3 levels were unchanged.
Structured PICO
PPopulationRats (model of isoproterenol-induced heart failure)
IInterventionIsoproterenol (5 mg/kg/day, intraperitoneally) for 1 week, followed by NOS inhibition (L-NAME) in isolated tissues
OOutcomeEffects of NOS inhibition on isolated atria and electrically paced left ventricular myocytes, and expression of NOS proteinssurrogate
In a rat model of isoproterenol-induced heart failure, NO does not sustain contractility of failing myocytes despite increased NO synthesis capacity, but may contribute to decreased basal heart rate.