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


Autoria(s): Camelo, J. S., Jr.; Martins, A. R.; Rosa, E.; Ramos, S. G.; Hehre, D.; Bancalari, E.; Suguihara, C.
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

04/11/2013

04/11/2013

2012

Resumo

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 AT(1) receptor (AT(1)-R) blocker L-158,809 (L) during 6 days of hypoxia (FiO(2) = 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 AT(1)-R in P animals during hypoxia compared to normoxic animals (C group, N = 5; P < 0.01 for all groups). AT(1)-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 AT(1)-R staining. Macrophages and pneumocytes showed moderate or strong iNOS and AT(1)-R staining, but C animals showed weak iNOS and AT(1)-R staining. Macrophages of L and P animals showed moderate and weak AT(2)-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 AT(1)-R blockade. We suggest that AT(1)-R blockade might act through AT(2)-R and/or Mas receptors and the nitrergic system in the lungs of hypoxemic newborn piglets.

University of Miami

FAPESP

Identificador

BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH, SAO PAULO, v. 45, pp. 163-171, FEB, 2012

0100-879X

http://www.producao.usp.br/handle/BDPI/37772

10.1590/S0100-879X2012007500014 

http://dx.doi.org/10.1590/S0100-879X2012007500014 

Idioma(s)

eng

Publicador

ASSOC BRAS DIVULG CIENTIFICA

SAO PAULO

Relação

BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH

Direitos

openAccess

Copyright ASSOC BRAS DIVULG CIENTIFICA

Palavras-Chave #NEWBORN ANIMALS #PULMONARY HYPERTENSION #ANGIOTENSIN II #ANGIOTENSIN RECEPTORS #HYPOXIA #NITRIC-OXIDE SYNTHASE #CONGENITAL DIAPHRAGMATIC-HERNIA #CONVERTING ENZYME #EXPRESSION #LUNG #ACTIVATION #INHIBITION #INOS #NO #VASOCONSTRICTION #BIOLOGY #MEDICINE, RESEARCH & EXPERIMENTAL
Tipo

article

original article

publishedVersion