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Vol. 6. Núm. A.
Actualización y futuro del óxido nítrico en el tratamiento de la enfermedad cardiovascular
Páginas 3A-20A (Marzo 2006)
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Vol. 6. Núm. A.
Actualización y futuro del óxido nítrico en el tratamiento de la enfermedad cardiovascular
Páginas 3A-20A (Marzo 2006)
Actualización y futuro del óxido nítrico en el tratamiento de la enfermedad cardiovascular
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Efectos del óxido nítrico sobre la función cardíaca
Effects of Nitric Oxide on Cardiac Function
Visitas
...
Juan Tamargo??
Autor para correspondencia
jtamargo@med.ucm.es

Correspondencia: Dr. J. Tamargo. Departamento de Farmacología. Facultad de Medicina. Universidad Complutense. Avda. Complutense, sn. 28040 Madrid. España.
, Ricardo Caballero, Ricardo Gómez, Lucía Núñez, Miguel Vaquero, Eva Delpón
Departamento de Farmacología. Facultad de Medicina. Universidad Complutense. Madrid. España
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El óxido nítrico (NO) liberado por prácticamente todas las células del corazón ejerce múltiples efectos sobre la función cardíaca. Modula las respuestas inotrópicas y cronotrópicas, el flujo de entrada de Ca++ y el ciclo del Ca++ en el retículo sarcoplásmico, la transmisión autonómica, la frecuencia cardíaca, la respiración mitocondrial, el consumo miocárdico de O2 y la eficiencia mecánica. El NO regula la contractilidad cardíaca en respuesta a la distensión e inhibe la relación fuerza-frecuencia y las respuesta a la estimulación β-adrenérgica. También mejora la distensibilidad ventricular y aumenta el trabajo latido en pacientes con miocardiopatía dilatada, y desempeña un importante papel en la fase tardía del precondicionamiento isquémico. Por último, el NO puede modular la actividad de los canales cardíacos, la arritmogénesis, la apoptosis y la función cardíaca en el miocardio insuficiente. Para realizar todas estas funciones, las NO sintasas (NOS) se localizan en microdominios de los cardiomiocitos en íntima vecindad con las vías de señalización que modulan. Sin embargo, es necesario conocer mejor los mecanismos implicados en la regulación y la localización celular de las NOS, así como las vías no enzimáticas de síntesis del NO, su localización y su inactivación en diversas situaciones fisipatológicas antes de que podamos trasladar las múltiples acciones del NO en una alternative terapéutica.

Palabras clave:
Óxido nítrico
Óxido nítrico sintasas
Contracción miocárdica
Frecuencia cardíaca
Abbreviations:
ACh
Akt
ASK-1
[Ca++]i
Ca++-Ca++M
CE
MCD
dP/dtmáx
GCs
IC
ICa++L
LPS
MVO2
NA
NO
NOS
PDE
PKA/G
PTDVI
RFF
RM2
RS
RyR2
SERCA2a
VI
XO

The nitric oxide (NO) that is released from almost all cardiac cells exerts numerous effects on cardiac function. These include the modulation of cardiac inotropic and chronotropic responses, sarcolemmmal calcium influx and sarcoplasmic reticulum calcium cycling, autonomic nerve transmission, heart rate, mitochondrial respiration, myocardial oxygen consumption, and myocardial energetics. NO regulates cardiac contractility in response to stretch, depresses the force-frequency relationship, and inhibits responses to ß-adrenergic stimulation. Moreover, it improves ventricular distensibility and increases stroke work in patients with dilated cardiomyopathy, and it plays an important role in the late phase of preconditioning. Finally, NO can modulate cardiac ion channels, arrhythmogenesis, apoptosis, and cardiac function in the failing heart. In order to perform these numerous functions, nitric oxide synthases (NOS) are spatially confined to different cardiomyocyte microdomains in close vicinity to second-messenger pathways. However, before we can develop alternative therapeutic strategies based on the effects of NO, we need to learn more about the mechanisms that regulate NOS activity and that determine the subcellular location of NOS, as well as about nonenzymatic NO formation and the storage and inactivation of NO within different cardiac cells under various physiopathological conditions.

Key words:
Nitric oxide
Nitric oxide synthases
Myocardial contraction
Heart rate
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