[Angiotensin II receptors in a rat model of hypobaric hypoxic pulmonary hypertension].
Hypoxic pulmonary hypertension is characterized by profound remodeling of the walls of small pulmonary arteries: endothelial swelling and proliferation of media and adventitia to a degree that may narrow the lumen. The molecular mechanism responsible for these changes is unknown. Recent studies have demonstrated the existence of a vascular and cardiac renin-angiotensin system. This system can induce hypertrophy and proliferation of aortic smooth muscle cells and cardiac muscle cells in animal models of systemic hypertension. In the present experiments, Northern blot analysis and a receptor binding assay specific to angiotensin II (Ang II) receptors was used to study the pulmonary renin angiotensin system in a rat model of hypobaric hypoxic pulmonary hypertension. mRNA transcripts for the Ang II receptor AT(1A) were constitutively expressed, and specific binding of Ang II to the receptors occurred in lung tissue of control rats that breathed ambient air. After 3 days of hypobaric hypoxia (380 Torr), the AT(1A) mRNA level and the index of Ang II receptors had increased, but right ventricular hypertrophy was not still evident. Ang II receptors were significantly increased after 14 days of hypoxia, when histological evidence of pulmonary hypertension was observed. In addition, the Ang II level in pulmonary tissue was higher after 14 days of hypoxia than in normal controls. These findings suggest that the renin-angiotensin system in pulmonary tissue was activated in these rats, and that it contributes to the morphological changes observed in hypoxic pulmonary hypertension.
Mikami
O
O
Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Nagaoka
I
I
Hasunuma
K
K
Takahashi
H
H
D000818:Animals; D001274:Atmospheric Pressure; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism*; D000860:Hypoxia / Q000150:complications*; D008168:Lung / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism*
D011945:Receptors, Angiotensin