Angiotensin II type 1 receptor blockade partially attenuates hypoxia-induced pulmonary hypertension in newborn piglets: Relationship with the nitrergic system

J. S. Camelo, A. R. Martins, E. Rosa, S. G. Ramos, D. Hehre, E. Bancalari, C. Suguihara

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The objective of this study was to observe possible interactions between the renin-angiotensin and nitrergic systems in chronic hypoxia-induced pulmonary hypertension in newborn piglets. Thirteen chronically instrumented newborn piglets (6.3 ± 0.9 days; 2369 ± 491 g) were randomly assigned to receive saline (placebo, P) or the AT1 receptor (AT1-R) blocker L-158,809 (L) during 6 days of hypoxia (FiO2 = 0.12). During hypoxia, pulmonary arterial pressure (Ppa; P < 0.0001), pulmonary vascular resistance (PVR; P < 0.02) and the pulmonary to systemic vascular resistance ratio (PVR/SVR; P < 0.05) were significantly attenuated in the L (N = 7) group compared to the P group (N = 6). Western blot analysis of lung proteins showed a significant decrease of endothelial NOS (eNOS) in both P and L animals, and of AT1-R in P animals during hypoxia compared to normoxic animals (C group, N = 5; P < 0.01 for all groups). AT1-R tended to decrease in L animals. Inducible NOS (iNOS) did not differ among P, L, and C animals and iNOS immunohistochemical staining in macrophages was significantly more intense in L than in P animals (P < 0.01). The vascular endothelium showed moderate or strong eNOS and AT1-R staining. Macrophages and pneumocytes showed moderate or strong iNOS and AT1-R staining, but C animals showed weak iNOS and AT1-R staining. Macrophages of L and P animals showed moderate and weak AT2-R staining, respectively, but the endothelium of all groups only showed weak staining. In conclusion, pulmonary hypertension induced by chronic hypoxia in newborn piglets is partially attenuated by AT1-R blockade. We suggest that AT1-R blockade might act through AT2-R and/or Mas receptors and the nitrergic system in the lungs of hypoxemic newborn piglets.

Original languageEnglish (US)
Pages (from-to)163-171
Number of pages9
JournalBrazilian Journal of Medical and Biological Research
Volume45
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • Angiotensin II
  • Angiotensin receptors
  • Hypoxia
  • Newborn animals
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Physiology
  • Biochemistry
  • Biophysics
  • Cell Biology

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