Prevention of increases in blood pressure and left ventricular mass and remodeling of resistance arteries in young New Zealand genetically hypertensive rats: the effects of chronic treatment with valsartan, enalapril and felodipine.
The relative efficacy of three antihypertensive drugs in the prevention of further elevation of blood pressure (BP) and cardiovascular structural remodeling in 4-week-old genetically hypertensive (GH) rats was studied by means of two complementary methods, stereology and myography. Four to 10-week-old GH rats were treated with valsartan (10 mg/kg/day), enalapril (10 mg/kg/day) or felodipine (30 mg/kg/day). Untreated GH and normotensive control rats of Wistar origin served as controls. Tail-cuff systolic SBP was measured weekly and left ventricular (LV) mass determined at the end of the experiment. Mesenteric resistance arteries (MRA) were either fixed by perfusion, embedded in Technovit and sections stained for stereological analysis, or mounted on a wire myograph for structural and functional measurements. BP and LV mass were significantly reduced by all drugs; decreases in BP and LV mass were smaller after felodipine treatment. Valsartan and enalapril caused a decrease in BP to normotensive control values. Felodipine kept BP at the 4-week level and prevented further rise with age. Valsartan caused hypotrophic outward remodeling of MRA, enalapril eutrophic outward remodeling and felodipine hypotrophic remodeling. Myograph measurements showed remodeling of the same order. While all drugs lowered the media/lumen ratio in GH to normal, the outward remodeling after valsartan and enalapril indicates that valsartan and enalapril might be more effective in reversing the inward remodeling of resistance arteries found in essential hypertension.
Ledingham
J M
JM
Department of Pharmacology, University of Otago, School of Medical Sciences, Dunedin, New Zealand. janet.ledingham@stonebow.otago.ac.nz
Phelan
E L
EL
Cross
M A
MA
Laverty
R
R
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure; D001835:Body Weight; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology*; D015736:Felodipine / Q000008:administration & dosage / Q000494:pharmacology*; D006352:Heart Ventricles / Q000473:pathology*; D006973:Hypertension / Q000473:pathology / Q000517:prevention & control*; D017379:Hypertrophy, Left Ventricular / Q000517:prevention & control*; D008638:Mesenteric Arteries / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D000959:Antihypertensive Agents; D013777:Tetrazoles; D004656:Enalapril; D000068756:Valsartan; D014633:Valine; D015736:Felodipine