IQUIMEFA   05518
INSTITUTO QUIMICA Y METABOLISMO DEL FARMACO
Unidad Ejecutora - UE
artículos
Título:
Autonomic regulation of pacemaker activity: role of heart nitric oxide synthases
Autor/es:
FELLET A.; BALASZCZUK A.; ARRANZ C.; LOPEZ COSTA J.; BOVERIS A.; BUSTAMANTE J.
Revista:
THE AMERICAN JOURNAL OF PHYSIOLOGY.
Editorial:
American Physiological Society
Referencias:
Lugar: Bethesda, EEUU; Año: 2006 vol. 291 p. 1246 - 1254
ISSN:
0002-9513
Resumen:
Autonomic regulation of pacemaker activity: role of heart nitric oxide
synthases. Am J Physiol Heart Circ Physiol 291: H1246H1254, 2006.
First published April 14, 2006; doi:10.1152/ajpheart.00711.2005.In
autonomic-blocked rats treated with NG-nitro-L-arginine methyl ester
(L-NAME, 7.5 mg/kg), heart rate increased 18% and mean arterial
pressure increased 48%. Thyroidectomy, along with autonomic blockade,
hampered the chronotropic response but did not modify the effect on
blood pressure. After 150 min of autonomic blockade, the experimental
end point, total nitric oxide (NO) production by heart NO synthases
(NOS) decreased 61%: from 54 to 21 nmol NO min -1g heart-1 .
Mitochondrial NOS (mtNOS) and sarcoplasmic reticulum endothelial
NOS activities decreased 74% and 52%, respectively. Mitocondria
isolated from whole heart showed a well-coupled oxidative phosphorylation
with high respiratory control and ADP-to-O ratios, decreased
mtNOS activity (5560%), and decreased mtNOS protein expression
(70%). Immunohistochemistry with anti-inducible NOS antibody linked
to gold particles localized mtNOS at the inner mitochondrial membranes.
Histochemical right atrial NOS (NADPH-diaphorase) decreased 55%
after heart denervation. The effects of autonomic denervation on the NO
system were partially prevented by thyroidectomy performed simultaneously
with autonomic blockade. Western blot analysis indicated a very
rapid mtNOS protein turnover (half time =120 min) with a process of
protein expression that was upregulated by thyroidectomy and a degradation
process that was downregulated by the autonomic nervous system.
The observations suggest that NO-mediated pathways contribute to
pacemaker heart activity, likely through the NO steady-state levels in the
right atrium and the whole heart.