Lung angiotensin receptor binding characteristics during the development of monocrotaline-induced pulmonary hypertension.
Alterations in lung angiotensin converting enzyme (ACE) activity in monocrotaline (MCT)-induced pulmonary hypertension in rats have suggested a pathophysiologic role for angiotensin II (AII) in pulmonary vascular remodeling. ACE inhibitors suppress MCT-induced pulmonary hypertension; however, losartan, an angiotensin type 1 (AT1) receptor antagonist, 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 [125I]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 hypertension, increased at 21 days post-MCT. Saturation binding isotherms revealed a single, high affinity site for [125I]AII binding in lung membranes from MCT-treated and control rats, with no change in receptor affinity or density during the development of pulmonary hypertension. Competition displacement binding demonstrated that the AT1 receptor predominates in lung membranes from control rats, with no alterations in AII receptor subtype distribution following MCT treatment. In summary, these results suggest that the AT1 receptor subtype predominates in rat lung and does not contribute to the development of MCT-induced pulmonary hypertension.
Cassis
L
L
Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA.
Shenoy
U
U
Lipke
D
D
Baughn
J
J
Fettinger
M
M
Gillespie
M
M
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001667:Binding, Competitive; D001713:Biphenyl Compounds / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000139:chemically induced*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008168:Lung / Q000378:metabolism*; D008297:Male; D016686:Monocrotaline; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D016686:Monocrotaline; D019808:Losartan