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01.10.2014 | Original Article

The soluble guanylyl cyclase activator BAY 60-2770 potently relaxes the pulmonary artery on congenital diaphragmatic hernia rabbit model

verfasst von: Julio Alejandro Rojas-Moscoso, Edson Antunes, Rebeca Rodrigues Figueira, Frances Lilian Gonçalves, Ana Leda Bertoncioni Simões, Lourenço Sbragia

Erschienen in: Pediatric Surgery International | Ausgabe 10/2014

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Abstract

Purpose

Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypertension which is often difficult to manage, and a significant cause of morbidity and mortality. In this study, we have used a rabbit model of CDH to evaluate the effects of BAY 60-2770 on the in vitro reactivity of left pulmonary artery.

Methods

CDH was performed in New Zealand rabbit fetuses (n = 10 per group) and compared to controls. Measurements of body, total and left lung weights (BW, TLW, LLW) were done. Pulmonary artery rings were pre-contracted with phenylephrine (10 μM), after which cumulative concentration–response curves to glyceryl trinitrate (GTN; NO donor), tadalafil (PDE5 inhibitor) and BAY 60-2770 (sGC activator) were obtained as well as the levels of NO (NO₃/NO₂).

Results

LLW, TLW and LBR were decreased in CDH (p < 0.05). In left pulmonary artery, the potency (pEC₅₀) for GTN was markedly lower in CDH (8.25 ± 0.02 versus 9.27 ± 0.03; p < 0.01). In contrast, the potency for BAY 60-2770 was markedly greater in CDH (11.7 ± 0.03 versus 10.5 ± 0.06; p < 0.01). The NO₂/NO₃ levels were 62 % higher in CDH (p < 0.05).

Conclusion

BAY 60-2770 exhibits a greater potency to relax the pulmonary artery in CDH, indicating a potential use for pulmonary hypertension in this disease.

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Titel: The soluble guanylyl cyclase activator BAY 60-2770 potently relaxes the pulmonary artery on congenital diaphragmatic hernia rabbit model
verfasst von: Julio Alejandro Rojas-Moscoso
Edson Antunes
Rebeca Rodrigues Figueira
Frances Lilian Gonçalves
Ana Leda Bertoncioni Simões
Lourenço Sbragia
Publikationsdatum: 01.10.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Surgery International / Ausgabe 10/2014
Print ISSN: 0179-0358
Elektronische ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-014-3561-3

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The soluble guanylyl cyclase activator BAY 60-2770 potently relaxes the pulmonary artery on congenital diaphragmatic hernia rabbit model

Abstract

Purpose

Methods

Results

Conclusion

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Conclusion

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