Sildenafil Inhibits Hypoxia-Induced Pulmonary Hypertension

Zhao, Lan; Mason, Nicola A.; Morrell, Nicholas W.; Kojonazarov, Baktybek; Садыков, А М; Maripov, Abdirashit; Миррахимов, М М; Aldashev, Almaz; Wilkins, Martin R.

doi:10.1161/hc2901.093117

Cited by 440 publications

(331 citation statements)

References 33 publications

Supporting

Mentioning

300

Contrasting

Unclassified

Order By: Relevance

“…A PDE5 é encontrada em maior concentração nos tecidos pulmonares e age diretamente na hidrólise da guanosina-monofosfato cíclico (GMPc), que é o mediador intracelular vascular pulmonar responsável pelas ações vasorrelaxantes e antimitogênicas em condi- ções de hipoxia alveolar. (7) O GMPc é ativado pela ligação com o óxido nítrico (NO) e com o peptídeo natriurético. Portanto, o sildenafil, por diminuir a ação da PDE5, aumenta significativamente as concentrações de GMPc, levando à vasodilatação pulmonar.…”

Section: Discussionunclassified

“…Tanto em estudos experimentais quanto em seres humanos, o sildenafil reduziu de forma significativa os ní-veis pressóricos da circulação pulmonar durante exposição à hipoxia, tanto aguda como cronicamente. (7) Em estudos recentes, (8) o sildenafil mostrou-se tão eficaz na redução da resistência vascular pulmonar quanto a inalação de óxido nítrico (NO). Mostrou, ainda, maior aumento do índice cardíaco e queda da pressão de oclusão da artéria pulmonar.…”

Section: Discussionunclassified

See 1 more Smart Citation

Resolução do "shunt" direita-esquerda após uso do sildenafil como tratamento de hipertensão pulmonar primária

et al. 2003

View full text Add to dashboard Cite

Hipertensão pulmonar primária é uma doença rara, progressiva e com alta mortalidade, cujo tratamento baseia-se em medicações de alto custo e pouco disponíveis em nosso meio. O sildenafil é um vasodilatador de fácil administração por via oral, com indicação primária para disfunção erétil e que recentemente tem sido descrito como opção terapêutica para a hipertensão pulmonar primária. Relata-se o caso de uma paciente de 21 anos com diagnóstico de hipertensão pulmonar primária, que apresentou piora abrupta da saturação de oxigênio, com abertura do forame oval e shunt direita-esquerda, evidenciados ao ecocardiograma. Foi introduzido sildenafil na dose de 225mg/dia com melhora progressiva da oxigenação e reversão do shunt após 40 dias. Os autores acreditam que o sildenafil seja uma opção no tratamento da hipertensão pulmonar primária, embora estudos clínicos que comprovem sua segurança e eficácia ainda sejam necessários.

show abstract

Section: Discussionunclassified

Resolução do "shunt" direita-esquerda após uso do sildenafil como tratamento de hipertensão pulmonar primária

et al. 2003

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

“…Control of the activity of sGC by nitric oxide (NO) has a major influence on the function of the neonatal and adult pulmonary circulation (15,35,39). In addition, alterations in the regulation of sGC by NO is thought to be a major factor influencing vascular function in multiple diseases, including pulmonary hypertension (39). While the role of superoxide in attenuating the regulation of sGC by NO has been extensively studied in multiple vascular diseases (14,23), other processes could be contributing factors to alterations in the sensitivity of sGC to regulation by NO.…”

Section: Introductionmentioning

confidence: 99%

Heme oxygenase-1 induction depletes heme and attenuates pulmonary artery relaxation and guanylate cyclase activation by nitric oxide

Mingone¹,

Ahmad²,

Gupte³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

This study examines in endothelium-denuded bovine pulmonary arteries the effects of increasing heme oxygenase-1 (HO-1) activity on relaxation and soluble guanylate cyclase (sGC) activation by nitric oxide (NO). A 24 hour organ culture with 0.1 mM cobalt chloride (CoCl 2 ) or 30 μM Coprotoporphyrin IX was developed as a method of increasing HO-1 expression. These treatments increased HO-1 expression and HO activity by ~2-4 fold, and lowered heme levels by 40-45%. Induction of HO-1 was associated with an attenuation of pulmonary arterial relaxation to the NOdonor spermine-NONOate. The presence of a HO-1 inhibitor 30 μM chromium mesoporphyrin during the 24 hour organ culture (but, not acute treatment with this agent) reversed the attenuation of relaxation to NO seen in arteries co-cultured with agents that increased HO-1. Relaxation to isoproterenol, which is thought to be mediated through cAMP, was not altered in arteries with increased HO-1. Inducers of HO-1 did not appear to alter basal sGC activity in arterial homogenates or expression of the β1-subunit of sGC. However, the increase in activity seen in the presence of 1 μM spermine-NONOate was attenuated in homogenates obtained from arteries with increased HO-1. Since arteries with increased HO-1 had decreased levels of superoxide detected by the chemiluminescence of 5 μM lucigenin, superoxide did not appear to be mediating the attenuation of relaxation to NO. These data suggest that increasing HO-1 activity depletes heme, and this is associated with an attenuation of pulmonary artery relaxation and sGC activation responses to NO.

show abstract

“…1 Thus, new treatment options have been investigated, including phosphodiesterase-5 inhibitors, such as sildenafil, which increases the concentration of cyclic guanosine m o n o p h o s p h a t e ( c G M P ) a n d c a u s e s p u l m o n a r y vasodilation. 4,5 Case report…”

Section: Introductionmentioning

confidence: 99%

Sildenafil no tratamento da hipertensão pulmonar após cirurgia cardíaca

Bentlin¹,

Saito²,

Luca³

et al. 2005

J. Pediatr. (Rio J.)

View full text Add to dashboard Cite

Objective: To report on the use of sildenafil for pulmonary hypertension treatment of a newborn patient after cardiac surgery.Description: A female, full term newborn infant with diagnosis of double outlet right ventricle, pulmonary hypoplasia and subaortic ventricular septal defect, was submitted to Blalock surgery in the first week of life. In postoperative the newborn had pulmonary hypertension and persistent hypoxia, without response to nitric oxide, but with improved oxygenation after continuous intravenous infusion of prostaglandin E1. After several failed attempts to discontinue prostaglandin E1, oral sildenafil was used. There was a decrease in pulmonary vascular resistance with consequent oxygenation improvement and 48 hours later it was possible to discontinue prostaglandin E1 infusion.Comments: Sildenafil can be an alternative therapy for pulmonary hypertension, especially when there is no response to conventional therapy.J Pediatr (Rio J). 2005;81(2):175-8: Sildenafil, pulmonary hypertension, prostaglandin.

show abstract

Sildenafil Inhibits Hypoxia-Induced Pulmonary Hypertension

Cited by 440 publications

References 33 publications

Resolução do "shunt" direita-esquerda após uso do sildenafil como tratamento de hipertensão pulmonar primária

Resolução do "shunt" direita-esquerda após uso do sildenafil como tratamento de hipertensão pulmonar primária

Heme oxygenase-1 induction depletes heme and attenuates pulmonary artery relaxation and guanylate cyclase activation by nitric oxide

Sildenafil no tratamento da hipertensão pulmonar após cirurgia cardíaca

Contact Info

Product

Resources

About