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

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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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Acknowledgments

Grant #471496/2011-1- the National Council for Scientific and Technological Development (CNPq).

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medical Sciences, University of Campinas-UNICAMP, Campinas, SP, Brazil

    Julio Alejandro Rojas-Moscoso & Edson Antunes

  2. Laboratory of Experimental Fetal Surgery “Michael R Harrison”, Division of Pediatric Surgery, Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo-USP, Av. Bandeirantes, 3900, Ribeirão Prêto, SP, 14048-900, Brazil

    Rebeca Rodrigues Figueira, Frances Lilian Gonçalves, Ana Leda Bertoncioni Simões & Lourenço Sbragia

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  1. Julio Alejandro Rojas-Moscoso
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Correspondence to Lourenço Sbragia.

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Rojas-Moscoso, J.A., Antunes, E., Figueira, R.R. et al. The soluble guanylyl cyclase activator BAY 60-2770 potently relaxes the pulmonary artery on congenital diaphragmatic hernia rabbit model. Pediatr Surg Int 30, 1031–1036 (2014). https://doi.org/10.1007/s00383-014-3561-3

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