Pulmonary vascular remodelling in hypoxic rats: effects of amlodipine, alone and with perindopril.
This study investigated whether pulmonary vascular remodelling in hypoxic pulmonary hypertensive rats (10% oxygen; 4 weeks) could be prevented by treatment, during hypoxia, with amlodipine (10 mg/kg/day, p.o.), either alone or in combination with the angiotensin converting enzyme inhibitor, perindopril (30 mg/kg/day, p.o.). Medial thickening of pulmonary arteries (30-500 microm o.d.) was attenuated by amlodipine whereas it was totally prevented by the combination treatment (amlodipine plus perindopril); neomuscularisation of small alveolar arteries (assessed from critical closing pressure in isolated perfused lungs) was not affected. Pulmonary vascular resistance (isolated perfused lungs) was reduced by both treatment regimes but only combination treatment reduced right ventricular hypertrophy. Thus, amlodipine has anti-remodelling properties in pulmonary hypertensive rats. The finding that combining amlodipine with another anti-remodelling drug produced effects on vascular structure that were additive raises the question of whether combination therapy with two different anti-remodelling drugs may be of value in the treatment of patients with hypoxic (and possibly other forms of) pulmonary hypertension.
Jeffery
T K
TK
Pulmonary Pharmacology Group, Department of Physiology and Pharmacology, The University of Queensland, St Lucia, Qld 4072, Brisbane, Australia.
Wanstall
J C
JC
D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D006352:Heart Ventricles / Q000473:pathology; D006976:Hypertension, Pulmonary / Q000503:physiopathology; D006984:Hypertrophy / Q000473:pathology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D020913:Perindopril / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D000959:Antihypertensive Agents; D017311:Amlodipine; D020913:Perindopril