Effects of Taurine on Myocardial cGMP/cAMP Ratio, Antioxidant Ability, and Ultrastructure in Cardiac Hypertrophy Rats Induced by Isoproterenol - Advances in Experimental Medicine and Biology - page 211

21.4 Discussion

In recent years, various functions have been attributed to taurine including osmoregu-
lation, antioxidation, and modulation of both calcium fluxes and protein phosphory-
lation. Taurine supplementation of the diet has been used in many clinical studies to
treat various pathological conditions. The results indicated that heart coefficient,
serum CK-MB, and myocardial cGMP and cAMP levels significantly increased
while the myocardial cGMP/cAMP ratio was significantly decreased in model group
by ISO-mediated myocardial cell hypertrophy, membrane damage, and phosphoryla-
tion. The creatine kinase system plays an important role in myocardial energy metab-
olism by maintaining ADP levels high at the mitochondria and low at sites of ATP
utilization (Wallimann et al. 1992 ). Increase in the activity of CK-MB in serum is a
marker of myocardial cell injury (Adams et al. 1993 ). It is well recognized that, in the
mammalian heart, adrenergic stimulation results in increases in the rates of force
development and relaxation (Grazyna et al. 1999 ). Most effects of b -adrenergic stim-
ulation are mediated by cAMP-dependent mechanisms. Increased cytosolic cAMP
activates cAMP-dependent protein kinases, which induce the phosphorylation of
membrane and contractile proteins. cAMP has a positive inotropic effect through an
increase in L-type calcium current (Balligand 1999 ) . Therefore cAMP-dependent
control of cardiac relaxation function is probably compromised in the hypertrophied
heart. In non-stimulated hearts, cGMP has been suggested to augment contractile
function at low concentrations, likely via cross talk with cAMP-dependent signaling,
inhibiting phosphodiesterase-3(PDE-3) and degradation of cAMP (Vila-Petroff et al.
1999 ). At higher concentrations, cGMP has a negative inotropic effect by antagoniz-
ing cAMP via protein kinase G (in mammals) or PDE-2 stimulation (in amphibians)
(Vila-Petroff et al. 1999 ) . With b-adrenergic activation, both cAMP and cGMP
synthesis increase, with the net effect of cGMP being negative on the inotropic
response (a brake) (Balligand 1999 ). Our results are in-line with the earlier study. It
has been reported that reducing cGMP level by NOS inhibition enhances b -adrener-
gic responsiveness (Hare et al. 1998 ). In addition to the negative inotropic action of
cGMP, it reduces oxygen consumption and offsets the development of cardiac hyper-
trophy (Calderone et al. 1998 ; Straznicka et al. 1999 ) . However, taurine administra-
tion would appear to attenuate the increase of heart coefficient, reduce CK-MB
leaked into the blood, inhibit the synthesis of cGMP and cAMP, and significantly
increase the cGMP/cAMP ratio in hypertrophied ventricular tissue. These indicated
that taurine could prevent cardiac hypertrophy by blocking the b -adrenergic stimula-
tion mediated by cAMP-/cGMP-dependent mechanisms and enhancing the negative
inotropic effect of cGMP against cardiac hypertrophy in vivo.
Reactive oxygen species (ROS) have emerged as key mediators of hypertrophic
remodeling and cardiac dysfunction. Recent years have witnessed accumulating evi-
dences for the involvement of oxidative stress in cardiac diseases including cardiac
hypertrophy (Sawyer et al. 2002 ; Itoh et al. 2008 ). Isoproterenol leads to oxidative
stress which contributes significantly to the pathophysiology of the myocardial disease
(Chattopadhyay et al. 2003 ). In the present study, the serum levels of SOD, GSH-Px,