Title of article :
The Nitric Oxide Donors, SNAP and DEA/NO, Exert a Negative Inotropic Effect in Rat Cardiomyocytes which is Independent of Cyclic GMP Elevation
Author/Authors :
Lakshman Sandirasegarane، نويسنده , , Jack Diamond، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 1999
Abstract :
The role of guanosine 3′,5′-cyclic monophosphate (cGMP) in the regulation of cardiac contractility remains controversial. The present study has examined the effects of high concentrations of the nitric oxide (NO) donors, S-nitroso-N-acetylpenicillamine (SNAP) and 1,1-diethyl-2-hydroxy-2-nitroso-hydrazine (DEA/NO), on cGMP levels and isoproterenol-induced increases in contractility in rat cardiomyocytes before and after selective inhibition of soluble guanylyl cyclase with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). In control myocytes, 100μ SNAP or 100μ DEA/NO increased cGMP levels by more than 15-fold at 2 and 6 min and produced marked attenuations of isoproterenol-mediated increases in maximal cell shortening over the same time period. The NO donors had no significant effect on basal cell shortening (in the absence of isoproterenol). Pretreatment of myocytes with 25μ ODQ for 30 min resulted in a complete blockade of the SNAP- or DEA/NO-induced increases in cGMP with no reversal of negative inotropy. ODQ did not affect basal contractility, basal cGMP levels or isoproterenol-induced increases in cell shortening. Furthermore, myocytes exposed to the cGMP analog, 8-bromo-cGMP (100μ ), did not exhibit significant differences in basal contractility or isoproterenol-induced increases in cell shortening. These results suggest that attenuation of cardiac contractility by NO donors in rat cardiomyocytes occurs by a mechanism independent of increases in cGMP levels.
Keywords :
S-nitroso-N-acetylpenicillamine (SNAP) , Nitric oxide (NO) , cyclic GMP , ODQ , Single cell contractility , Ventricular myocytes.
Journal title :
Journal of Molecular and Cellular Cardiology
Journal title :
Journal of Molecular and Cellular Cardiology