Role of chymase-dependent angiotensin II formation in monocrotaline-induced pulmonary hypertensive rats.
Angiotensin II-forming chymase is expressed in the pulmonary arteries of the monocrotaline-induced pulmonary hypertensive rats, but its actual role is unclear. We studied chymase-dependent angiotensin II formation in the pulmonary arteries of the monocrotaline-induced pulmonary hypertensive rats and observed the effects of an angiotensin II receptor blocker on vascular remodeling. Four weeks after the administration of monocrotaline (60 mg/kg, s.q.), echocardiographic, hemodynamic, morphometric and biochemical analyses were performed. Age-matched rats were used as controls. To evaluate the effects of an angiotensin II receptor blocker, 2 wk after beginning of monocrotaline treatment, the rats were given candesartan (10 mg/kg per day) or placebo for 2 wk. In the monocrotaline-induced pulmonary hypertensive rats, the elevated systolic pulmonary arterial pressure and right ventricular hypertrophy were observed. Medial hypertrophy of lung arterioles was also observed. Chymase activity and angiotensin II concentration, but not angiotensin-converting enzyme activity, were significantly increased in the lung. In the angiotensin II receptor blocker-treated group, both systolic pulmonary arterial pressure and right ventricular hypertrophy were significantly reduced, and arteriolar hypertrophy was also prevented. Thus, angiotensin II-forming chymase may play a role in the proliferation of the medial layer in the lung arterioles of monocrotaline-induced pulmonary hypertensive rats.
Kishi
Kanta
K
Department of Pharmacology, Osaka Medical College, Takatsuki City, Japan .
Jin
Denan
D
Takai
Shinji
S
Muramatsu
Michiko
M
Katayama
Hiroshi
H
Tamai
Hiroshi
H
Miyazaki
Mizuo
M
D000804:Angiotensin II / Q000032:analysis / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D049109:Cell Proliferation; D053818:Chymases; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D016686:Monocrotaline; D007703:Peptidyl-Dipeptidase A / Q000032:analysis / Q000378:metabolism; D011651:Pulmonary Artery / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000032:analysis; D012697:Serine Endopeptidases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D017540:Tunica Media / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D016686:Monocrotaline; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; D053818:Chymases; C081643:candesartan