Abstract: The dose-response relationship of sildenafil effects on cardiac function is not completely
elucidated. The aim of this study was to assess the effects of different doses of sildenafil on coronary
flow and oxidative stress in isolated rat hearts. Coronary flow and markers of oxidative stress,
including nitrite outflow, and superoxide anion production in coronary effluent, were determined for
isolated rat hearts. The experiments were performed during control conditions and in the presence
of sildenafil (10, 20, 50, 200 nM) alone or with Nω-nitro-L-arginine monomethyl ester (L-NAME)
(30 µM). Sildenafil was shown to result in a significant increase in coronary flow at lower coronary
perfusion pressure (CPP) values at all administered doses, whereas, with an increase in CPP, a
reduction in coronary flow was observed. An increase in nitric oxide (NO) was most pronounced in
the group treated with the lowest dose of sildenafil at the highest CPP value. After the inhibition
of the NO-cyclic guanosine monophosphate (cGMP) signaling (NOS) system by L-NAME, only a
dose of 200 nM sildenafil was high enough to overcome the inhibition and to boost release of O2
−.
That effect was CPP-dependent, with statistical significance reached at 80, 100 and 120 mmHg. Our
findings indicate that sildenafil causes changes in heart vasculature in a dose-dependent manner,
with a shift from a vasodilatation effect to vasoconstriction with a pressure increase. The highest dose
administered is capable of producing superoxide anion radicals in terms of NOS system inhibition.
