Diverse effects of Ace inhibitors and angiotensin II receptor antagonists on prevention of cardiac hypertrophy and collagen distribution in spontaneously hypertensive rats.
This study has compared the effects of two structurally different angiotensin converting enzyme inhibitors (ACEis) such as zofenopril (Zof, with sulfhydrylic group) and lisinopril (Lis, with carboxylic group) and an angiotensin II AT(1) receptor antagonist (losartan, Los) on the prevention of cardiac hypertrophy and collagen distribution in spontaneously hypertensive rats (SHRs). The SHRs were untreated or received: Zof (10 mg/kg/day), Lis (10 mg/kg/day) or Los (20 mg/kg/day) in drinking water starting at 4 weeks of age. At 8, 16 and 24 weeks of age, 8 rats/group were sacrificed for determination of blood pressure, cardiac hypertrophy and collagen distribution. All treatments significantly decreased blood pressure and cardiac indices, expressed as the ventricles to body weight ratio, both variables being significantly correlated. Total ventricular collagen content was similarly decreased in all treated groups. Zof significantly increased the expression of collagen type III and normalized the collagen type I/III ratio. These results suggest that the effects of these drugs on different types of collagen are independent from angiotensin II formation. Similar findings obtained with captopril seem to indicate that the antioxidant sulfhydrylic group of these ACEis can play a role in the distribution of collagen during cardiac hypertrophy.
Gagnon
C
C
Department of Pharmacology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montreal, Quebec, Canada H3C 3J7.
Legault
F
F
Geraldes
P
P
Tanguay
J-F
JF
Lambert
C
C
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D003094:Collagen / Q000378:metabolism*; D006339:Heart Rate; D006352:Heart Ventricles / Q000737:chemistry; D017379:Hypertrophy, Left Ventricular / Q000517:prevention & control*; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin; D014018:Tissue Distribution / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D003094:Collagen