LUNG ANGIOTENSIN RECEPTOR-BINDING CHARACTERISTICS DURING THE DEVELOPMENT OF MONOCROTALINE-INDUCED PULMONARY-HYPERTENSION

Alterations in lung angiotensin converting enzyme (ACE) activity in mo nocrotaline (MCT)-induced pulmonary hypertension in rats have suggeste d a pathophysiologic role for angiotensin II (AII) in Pulmonary vascul ar remodeling. ACE inhibitors suppress MCT-induced pulmonary hypertens ion; however, losartan, an angiotensin type 1 (AT1) receptor antagonis t, was without impact. The present study examined AII receptor binding characteristics by radioligand binding during the development of MCT- induced pulmonary hypertension. Saturation binding isotherms for [I-12 5]AII binding to membrane preparations from rat lung were performed at 4, 10, and 21 days following a single injection of MCT (60 mg/kg) or saline vehicle. Right ventricular hypertrophy, an index of pulmonary h ypertension, increased at 21 days post-MCT. Saturation binding isother ms revealed a single, high affinity site for [I-125]AII binding in lun g membranes from MCT-treated and control rats, with no change in recep tor affinity or density during the development of pulmonary hypertensi on Competition displacement binding demonstrated that the AT1 receptor predominates in lung membranes from control rats, with no alterations in AT1 receptor subtype distribution following MCT treatment. In summ ary, these results suggest that the AT1 receptor subtype predominates in rat lung and does not contribute to the development of MCT induced pulmonary hypertension. (C) 1991 Elsevier Science Inc.