Abstract

CAMELO JR., J.S. et al. Angiotensin II type 1 receptor blockade partially attenuates hypoxia-induced pulmonary hypertension in newborn piglets: relationship with the nitrergic system. Braz J Med Biol Res [online]. 2012, vol.45, n.2, pp. 163-171.  Epub Feb 09, 2012 ISSN 1414-431X.  http://dx.doi.org/10.1590/S0100-879X2012007500014.

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.

Keywords : Newborn animals; Pulmonary hypertension; Angiotensin II; Angiotensin receptors; Hypoxia.