Hemodynamic effects of sildenafil interaction with a nitric oxide donor compound in a dog model of acute pulmonary embolism

Sildenafil attenuates acute pulmonary embolism (APE)-induced pulmonary hypertension. However, the hemodynamic effects of sildenafil in combination with other vasodilators during APE have not been examined yet. In the present study, we examined the hemodynamic effects of combined diethylenetriamine/nonoate (DETA-NO, 1 μMol kg− 1, i.v.) and sildenafil (0.25 mg/kg, i.v.) in an anesthetized dog model of APE. Plasma nitrite/nitrate (NOx) and cyclic GMP concentrations were determined using an ozone-based chemiluminescence assay and a commercial enzyme immunoassay, respectively. We found that this dose of DETA-NO did not attenuate APE-induced pulmonary hypertension. However, significant decreases in mean pulmonary artery pressure were observed 15, 30 and 45 min after the administration of sildenafil alone or after the combined administration of DETA-NO and sildenafil (all P < 0.05). No significant differences among groups were observed in the respiratory parameters. While DETA-NO significantly increased NOx concentrations by approximately 4 μM, cyclic GMP concentrations increased only when sildenafil was administered (all P < 0.05). These results show that the combined administration of 1 μMol kg− 1 of DETA-NO and sildenafil is not advantageous compared with sildenafil alone, thus suggesting that sildenafil alone produced maximum attenuation of APE-induced pulmonary hypertension, as far as the NO-cGMP pathway is concerned.