Vitamin C and quinapril abrogate LVH and endothelial dysfunction in aortic-banded guinea pigs.
Left ventricular hypertrophy (LVH) is a cardiovascular risk factor. A possible role for endothelial dysfunction in this condition was investigated in a Dunkin-Hartley guinea pig aortic-banded pressure overload-induced model of LVH. Aortic banding produced significant elevation of fore- and hindlimb blood pressure (BP), heart-to-body weight ratios, plasma angiotensin II (ANG II), endothelin-1 (ET-1), tumor necrosis factor-alpha (TNF-alpha) levels, and coronary microvascular endothelial cell (CMEC) NAD(P)H-dependent superoxide (O) production, and a significant decrease in basal and stimulated CMEC cGMP levels. Treatment of aortic-banded animals with the angiotensin-converting enzyme inhibitor quinapril and the antioxidant vitamin C, either alone or in combination, did not affect BP but caused a significant inhibition of the increases in the heart-to-body weight ratio, ANG II, ET-1, and TNF-alpha levels, and O production and restored cGMP responses to levels comparable with sham-operated animals. These data suggest that quinapril and vitamin C are capable of inhibiting LVH development due to pressure overload via mechanisms that involve the inhibition of oxidative stress, an improvement in coronary endothelial function, and increased nitric oxide bioavailability.
Bell
J P
JP
Department of Pharmacology, Therapeutics, and Toxicology and Sir Geraint Evans Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, United Kingdom.
Mosfer
S I
SI
Lang
D
D
Donaldson
F
F
Lewis
M J
MJ
D000818:Animals; D001024:Aortic Valve Stenosis / Q000150:complications / Q000503:physiopathology; D001205:Ascorbic Acid / Q000627:therapeutic use*; D001794:Blood Pressure; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D006168:Guinea Pigs; D006973:Hypertension / Q000150:complications / Q000209:etiology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000209:etiology; D007546:Isoquinolines / Q000627:therapeutic use*; D008297:Male; D009243:NAD / Q000502:physiology; D009249:NADP / Q000502:physiology; D000077583:Quinapril; D013481:Superoxides / Q000378:metabolism; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D009243:NAD; D013481:Superoxides; D009249:NADP; D001205:Ascorbic Acid; D000077583:Quinapril