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, 1microMol kg(-1), i.v.) and sildenafil (0.25mg/kg, i.v.) in an anesthetized dog model of APE. Plasma nitrite/nitrate (NO(x)) 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 45min 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 NO(x) concentrations by approximately 4microM, cyclic GMP concentrations increased only when sildenafil was administered (all P<0.05). These results show that the combined administration of 1microMol 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.
Dias-Junior
Carlos A
CA
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil, 14049-900.
Tanus-Santos
Jose E
JE
D000818:Animals; D001794:Blood Pressure; D006152:Cyclic GMP / Q000097:blood; D004195:Disease Models, Animal; D004285:Dogs; D004347:Drug Interactions; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009566:Nitrates / Q000097:blood; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009573:Nitrites / Q000097:blood; D010879:Piperazines / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000502:physiology; D011655:Pulmonary Embolism / Q000139:chemically induced / Q000503:physiopathology*; D011687:Purines; D012119:Respiration / Q000187:drug effects; D000068677:Sildenafil Citrate; D013450:Sulfones; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D006152:Cyclic GMP