Related Experiment Videos
Positive inotropic effect of nitric oxide in myocardium
P Mohan1, S U Sys, D L Brutsaert
1Department of Physiology and Medicine, University of Antwerp (RUCA), Belgium.
Insights
Nitric oxide (NO) has complex effects on heart muscle. While low levels may preserve function, high levels can depress cardiac performance, depending on the condition of the endocardial endothelium.
Area of Science:
- Cardiovascular Physiology
- Endothelial Function
- Cardiac Pharmacology
Background:
- The cardiac endothelium releases factors influencing cardiac muscle performance.
- Nitric oxide (NO), a key endothelial factor, modulates vascular smooth muscle via cyclic GMP (cGMP).
- Previous studies on NO's inotropic effects show conflicting results.
Purpose of the Study:
- To investigate the myocardial effects of NO-releasing agents and related compounds.
- To clarify the role of NO and cGMP in modulating cardiac contractility.
- To examine the influence of endocardial endothelium integrity on NO's effects.
Main Methods:
- Isolated cat papillary muscle preparations were used.
- Experiments involved NO donors (SNP, SIN-1, SNAP), a cGMP analogue (8-bromo-cGMP), and a phosphodiesterase inhibitor (zaprinast).
- Effects were assessed in muscles with intact and damaged endocardial endothelium, with and without methylene blue.
Main Results:
- SNP and SIN-1 showed concentration-dependent positive inotropic effects in muscles with damaged endothelium, but negative effects with intact endothelium.
- NO-induced inotropic effects were attenuated by methylene blue, indicating cGMP involvement.
- SNAP and 8-bromo-cGMP produced biphasic responses (positive at low, negative at high concentrations).
- Zaprinast induced a concentration-dependent positive inotropic effect.
Conclusions:
- Basal NO release and modest cGMP elevation may preserve myocardial function.
- Elevated cGMP levels (pathological) can depress cardiac function.
- Endocardial endothelium integrity significantly influences the inotropic effects of NO.
Abstract:
Cardiac endothelium modulates underlying cardiac muscle performance probably by releasing certain regulatory factors. Nitric oxide (NO), which accounts for the biological activity of the vascular endothelium-derived relaxing factor and relaxes vascular smooth muscle by elevating intracellular cyclic GMP (cGMP), may be involved in this cardiac modulation. Many recent studies have examined inotropic effects of NO utilizing NO donors and NO-synthase inhibitors, both in vitro and in vivo, with apparently contradictory results. We examined the myocardial effects of NO-releasing nitrovasodilators (sodium nitroprusside (SNP), SIN-1 and S-nitrosoacetyl penicillamine (SNAP)), a cGMP analogue, 8-bromo-cGMP, and the cGMP phosphodiesterase inhibitor zaprinast, in isolated cat papillary muscle. A novel concentration-dependent positive inotropic effect of SNP and SIN-1 in muscles with damaged endocardial endothelium (EE) was observed which contrasted to their negative inotropic effect in muscles with intact EE. Both NO-induced positive and negative inotropic effects were attenuated by methylene blue, suggesting a role for cGMP. Concentration response curves with addition of SNAP and 8-bromo-cGMP resulted in a biphasic inotropic response. While administration of low concentrations of SNAP and 8-bromo cGMP induced a positive inotropic effect, higher concentrations induced a negative inotropic effect. Administration of zaprinast caused a monophasic concentration-dependent positive inotropic effect. We conclude that basal release of NO and consequent modest (physiological?) elevation in cGMP may preserve myocardial function, while large (pathological?) increases would depress myocardial function.