Stimulation of nitric oxide-sensitive soluble guanylate cyclase in monocrotaline-induced pulmonary hypertensive rats.
Life Sci
; 203: 203-209, 2018 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-29705351
ABSTRACT
AIMS:
In this study, we examined whether a disruption in the balance between nitric oxide (NO)-sensitive and -insensitive soluble guanylate cyclase (sGC) is observed in pulmonary hypertension (PH) and whether treatment with NO-enhancing drugs can halt disease progression. MAINMETHODS:
Rats were injected subcutaneously with saline or 60â¯mg/kg monocrotaline (MCT). At 14â¯days after injection, the vascular reactivity of isolated extralobar pulmonary arteries was assessed by organ chamber technique. In a separate experiment, isosorbide mononitrate (0.3 or 1â¯g/L) or sodium nitrite (30 or 300â¯mg/L) was administered in drinking water for the last 14â¯days (from day 15 to day 28), and their therapeutic potential was evaluated. KEYFINDINGS:
The NO-sensitive sGC stimulant BAY 41-2272 and the NO-insensitive sGC stimulant BAY 60-2770 both relaxed the pulmonary arteries, which was comparable between saline- and MCT-injected rats. Treatment with isosorbide mononitrate suppressed the MCT-induced right ventricular systolic pressure (RVSP) elevation and pulmonary arterial medial thickening but not right ventricular hypertrophy. However, the beneficial effects on RVSP and pulmonary vascular remodeling were not observed when a high dose was administered. The same results were obtained following the sodium nitrite treatment. Interestingly, NO-enhancing drugs did not increase plasma nitrite plus nitrate levels at a dose that provided the greatest therapeutic advantage.SIGNIFICANCE:
These findings suggest that the balance between NO-sensitive and -insensitive sGC is not disrupted in the early stage of MCT-induced PH. Furthermore, supplementation with an adequate amount of NO may be a useful therapy to prevent the progression of PH.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artéria Pulmonar
/
Pressão Sanguínea
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Broncodilatadores
/
Monocrotalina
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Guanilil Ciclase Solúvel
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Hipertensão Pulmonar
/
Óxido Nítrico
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article