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Angiotensin II receptor expression and inhibition in the chronically hypoxic rat lung

1996; Wiley; Volume: 119; Issue: 6 Linguagem: Inglês

10.1111/j.1476-5381.1996.tb16025.x

1476-5381

Lan Zhao, Rida Al‐Tubuly, Abdelkrim Sebkhi, Ali Akbar Owji, Derek J. Nunez, Martin R. Wilkins,

Nitric Oxide and Endothelin Effects

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 [125I]-[Sar1, Ile8]AII binding capacity was increased in lung membranes from rats exposed to hypoxia (10% fractional inspired O2) for 7 days compared to normal rats (Bmax 108 ± 12 vs 77 ± 3 fmol mg−1protein; P < 0.05), with no significant change in dissociation constant. Competition with specific AII receptor subtype antagonists demonstrated that AT1 is the predominant subtype in both normal and hypoxic lung. 3 Rats treated intravenously with the AT1 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 AT1 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 AT1 receptor, has a role in the early pathogenesis of hypoxia-induced pulmonary hypertension in the rat.