Effects of Ro 40-5967, a new calcium antagonist, and enalapril on cardiac remodeling in renal hypertensive rats.
The goal of the present study was to compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (enalapril) and a long-acting calcium antagonist (Ro 40-5967) on cardiac remodeling secondary to renovascular hypertension. For this purpose, two kidney-one clip (2K-1C) hypertensive rats, 6 weeks after renal artery clipping, were either untreated or treated for 5 weeks with equihypotensive doses of enalapril (3 mg/kg/day) and Ro 40-5967 (30 mg/kg/day). At the end of the treatment period, cardiac weight, maximum coronary blood flow ([MCBF], measured in isolated perfused hearts), and interstitial and perivascular collagen volume fraction (measured by morphometry) were evaluated in all rats. Both drugs similarly decreased arterial blood pressure (ABP) for 24 h. Enalapril was more effective than Ro 40-5967 in inducing regression of cardiac hypertrophy. MCBF was decreased in untreated hypertensive rats and was increased to the same extent by both treatments, although not normalized. Interstitial cardiac collagen content after 11 weeks of hypertension was not increased in untreated hypertensive rats. In contrast, the collagen volume fraction measured in the perivascular area was increased in untreated hypertensive rats and this increase was not significantly suppressed by either enalapril or Ro 40-5967. These results show that cardiac hypertrophy, decrease in MCBF and increase in myocardial collagen content, do not evolve in parallel in 2K-1C hypertensive rats. Two antihypertensive treatments, enalapril and Ro 40-5967, increased MCBF to the same extent but had different effects on cardiac hypertrophy despite having equal antihypertensive efficacy.
Véniant
M
M
Pharma Division, F. Hoffmann-La Roche, Basel, Switzerland.
Clozel
J P
JP
Heudes
D
D
Banken
L
L
Ménard
J
J
D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects; D004656:Enalapril / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020748:Mibefradil; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D013764:Tetrahydronaphthalenes; D020748:Mibefradil; D004656:Enalapril