Sildenafil improves the beneficial haemodynamic effects of intravenous nitrite infusion during acute pulmonary embolism
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Acute pulmonary embolism produces acute pulmonary hypertension, which can be counteracted by activating the nitric oxide-cyclic guanosine 3',5'-monophosphate (cGMP) pathway. While previous studies have shown that sildenafil (an inhibitor of cGMP-specific phosphodiesterase type 5) or nitrite (a storage molecule for nitric oxide) produces beneficial effects during acute pulmonary embolism, no previous study has examined whether the combination of these drugs can produce additive effects. Here, we expand previous findings and examine whether sildenafil enhances the beneficial haemodynamic effects produced by a low-dose infusion of nitrite in a dog model of acute pulmonary embolism. Haemodynamic and arterial blood gas evaluations were performed in non-embolized dogs treated with saline (n = 4), and in embolized dogs (intravenous injections of microspheres) that received nitrite (6.75 micromol/kg intravenously over 15 min. followed by 0.28 micromol/kg/min.) and sildenafil (0.25 mg/kg over 30 min.; n = 8), or nitrite followed by saline (n = 8), or saline followed by sildenafil (n = 7), or only saline (n = 8). Plasma thiobarbituric acid-reactive substances (TBARS) concentrations were determined using a fluorometric method. Acute pulmonary embolism increased pulmonary artery pressure by approximately 24 mmHg. While the infusion of nitrite or sildenafil infusions reversed this increase by approximately 42% (both P < 0.05), the combined infusion of both drugs reversed this increase by approximately 58% (P < 0.05). Similar effects were seen on the pulmonary vascular resistance index. Nitrite or sildenafil alone produced no significant hypotension. However, the combined infusion of both drugs caused transient hypotension (P < 0.05). Both drugs, either alone or combined, blunted the increase in TBARS concentrations caused by acute pulmonary embolism (all P < 0.05). These results suggest that sildenafil improves the beneficial haemodynamic effects of nitrite during acute pulmonary embolism.
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Nitrite infusions attenuated the pulmonary hypertension caused by acute pulmonary thromboembolism, and this effect was associated with lower lipid peroxidation.
“Nitrite infusions attenuated the pulmonary hypertension caused by acute pulmonary thromboembolism and this effect was associated with lower lipid peroxidation [21,23].”
From Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension (2011) · cites this paper as [23]
Nitrite has antioxidant effects in an animal model of acute pulmonary thromboembolism.
“we have previously shown antioxidant effects exerted by nitrite in an animal model of acute pulmonary thromboembolism [21,23].”
From Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension (2011) · cites this paper as [23]
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References 25 · Cited by 30
- Authors
- Dias‐Junior, C. A., Montenegro, M. F., Florencio, B. C., & Tanus‐Santos, J. E.
- Affiliations
- Universidade de São Paulo (BR)
- Venue
- Basic & Clinical Pharmacology & Toxicology
- Publisher
- Wiley
- Published
- 2008-09-16
- Volume
- 103
- Issue
- 4
- Pages
- 374-379
- ISSN
- 1742-7835 (ISSN-L)
- 1742-7843
- OpenAlex
- W2026730383
- Cited by
- 30
- References
- 25
- Citations by year
- 2025: 1 · 2023: 1 · 2021: 2 · 2019: 4 · 2015: 2 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Basic & Clinical Pharmacology & Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- Funders
- Pfizer
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Topics
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cardiovascular and Diving-Related Complications
- Keywords
- sildenafil, nitrite, acute pulmonary embolism, pulmonary hypertension, nitric oxide, cGMP pathway, phosphodiesterase-5 inhibition, pulmonary vascular resistance, hemodynamic effects, oxidative stress, TBARS, combination therapy, hypotension, microsphere embolism
- MeSH terms
- Sildenafil Citrate, Acute Disease, Animals, Blood Pressure, Disease Models, Animal, Dogs, Drug Synergism, Drug Therapy, Combination, Female, Hemodynamics, Hypertension, Pulmonary, Infusions, Intravenous, Lipid Peroxides, Male, Phosphodiesterase Inhibitors, Piperazines, Pulmonary Artery, Pulmonary Embolism, Purines, Respiration, Sodium Nitrite, Sulfones, Vascular Resistance
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