Kr. Shah et al., MECHANISMS OF INOTROPIC RESPONSES OF THE ISOLATED RAT HEARTS TO VANADATE, International journal of cardiology, 52(2), 1995, pp. 101-113
In view of the invariable development of insulin resistance in differe
nt types of cardiovascular diseases, considerable attention has been f
ocussed on vanadate because of its ability to exert insulin-like effec
ts in the body. Since vanadate, like insulin, has been shown to exert
a beneficial effect in diabetic cardiomyopathy, this study was underta
ken to examine the mechanisms of its action on the heart. Vanadate, at
5-10 mu M concentrations, produced a positive inotropic effect in the
isolated perfused rat heart, whereas at higher concentrations (20 mu
M), it decreased the contractile force development. The positive inotr
opic effect of 10 mu M vanadate was not affected by the pretreatment o
f animals with reserpine as well as the presence of propranolol or phe
noxybenzamine in the perfusion medium. The increase in contractile for
ce development due to vanadate at low (0.3-0.6 mM) concentrations of C
a2+ was markedly augmented, but this agent produced a negative inotrop
ic action at high concentrations of Ca2+ (2.0-3.0 mM). Preperfusion of
hearts with verapamil enhanced the positive inotropic effect ofvanada
te whereas hearts preperfused with ouabain, low sodium or amiloride sh
owed negative inotropic effects of vanadate. Vanadate was found to inh
ibit sarcoplasmic reticular Ca2+-pump and sarcolemmal Ca2+-pump as wel
l as Na+-K+-ATPase activities but the sarcolemmal effects were evident
at lower concentrations in comparison to that on the sarcoplasmic ret
iculum, The actions of vanadate on membrane Ca2+ transport and ATPase
systems were specific since this agent exerted no effect on sarcolemma
l Na+-Ca2+ exchange or myofibrillar ATPase activities, In isolated car
diomyocytes suspended in buffer containing 0.5 or 1.0 mM Ca2+, vanadat
e increased the intracellular concentration of Ca2+; this increase in
intracellular Ca2+ was more pronounced at 0.5 mM Ca2+. These results i
ndicate that increased intracellular concentration of Ca2+ due to inhi
bition of sarcolemmal Na+-K+-ATPase and sarcolemmal Ca2+-pump may be t
he primary mechanism of the positive inotropic action of vanadate in t
he heart, It is suggested that vanadate may serve as an inotropic agen
t and that this mechanism may contribute towards its beneficial effect
s on cardiac dysfunction in different cardiovascular diseases.