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Angiotensin II receptor expression and inhibition in the chronically hypoxic rat lung
Author(s) -
Zhao Lan,
AlTubuly Rida,
Sebkhi Abdelkrim,
Owji Ali A.,
Nunez Derek J.R.,
Wilkins Martin R.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb16025.x
Subject(s) - right ventricular hypertrophy , medicine , pulmonary hypertension , endocrinology , angiotensin ii , hypoxia (environmental) , lung , angiotensin ii receptor type 1 , pulmonary artery , muscle hypertrophy , ventricle , receptor , chemistry , oxygen , organic chemistry
1 Angiotensin II (All) binding density and the effect of chronic All receptor blockade were examined in the rat model of hypoxia‐induced pulmonary hypertension. 2 [ 125 I]‐[Sar 1 , Ile 8 ]AII binding capacity was increased in lung membranes from rats exposed to hypoxia (10% fractional inspired O 2 ) for 7 days compared to normal rats ( B max 108 ± 12 vs 77 ± 3 fmol mg −1 protein; P < 0.05), with no significant change in dissociation constant. Competition with specific AII receptor subtype antagonists demonstrated that AT 1 is the predominant subtype in both normal and hypoxic lung. 3 Rats treated intravenously with the AT 1 antagonist, GR138950C, 1 mg kg −1 day −1 rather than saline alone during 7 days of exposure to hypoxia developed less pulmonary hypertension (pulmonary arterial pressure: 21.3 ± 1.7 vs 28.3 ± 1.1 mmHg; P < 0.05), right ventricular hypertrophy (right/left ventricle weight ratio: 0.35 ±0.01 vs 0.45 ± 0.01; P < 0.05) and pulmonary artery remodelling (abundance of thick‐walled pulmonary vessels: 9.6 ± 1.4% vs 20.1 ±0.9%; P < 0.05). 4 The reduction in cardiac hypertrophy and pulmonary remodelling with the AT 1 antagonist was greater than that achieved by a dose of sodium nitroprusside (SNP) that produced a comparable attenuation of the rise in pulmonary arterial pressure during hypoxia. 5 The data suggest that AII, via the AT 1 receptor, has a role in the early pathogenesis of hypoxia‐induced pulmonary hypertension in the rat.