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The Effects of Different Doses of Sildenafil on Coronary Blood Flow and Oxidative Stress in Isolated Rat Hearts

2023; Multidisciplinary Digital Publishing Institute; Volume: 16; Issue: 1 Linguagem: Inglês

10.3390/ph16010118

1424-8247

Nada Banjac, Velibor Vasović, Nebojša Stilinović, Ana Tomás, Lucija Vasović, Nikola Martić, Dušan Prodanović, Vladimir Jakovljević,

Cardiac Arrhythmias and Treatments

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 O