title: Cardioprotective action of perindopril versus candesartan in renovascular hypertensive rats.
abstract: We investigated the effects of an angiotensin-converting enzyme inhibitor and an angiotensin II type 1 receptor blocker on cardiac hypertrophy in rats with renovascular hypertension. Renovascular hypertensive (Goldblatt) rats were surgically prepared from Wistar rats. Four weeks later, the rats showed a significant increase in blood pressure. At high doses, both the perindopril (1 mg/kg/day) and the candesartan (2 mg/kg/day) decreased the systolic pressure in these rats to the level of control Wistar rats. At low doses (perindopril 0.1 mg/kg/day and candesartan 0.1 mg/kg/day), these drugs lowered blood pressure to 85% of that in hypertensive rats. Echocardiographic and morphological studies revealed severe cardiac hypertrophy and fibrosis in untreated Goldblatt rats. High-dose treatment with both drugs suppressed the progression of hypertrophy and fibrosis. Also, low-dose perindopril prevented cardiac hypertrophy and fibrosis. In contrast, at the same levels of blood-pressure reduction, low-dose candesartan did not prevent cardiac fibrosis nor the upregulation of cardiac collagen types I and III mRNA observed in untreated Goldblatt rats. Atrial natriuretic peptide mRNA was up-regulated in untreated Goldblatt rats. These changes were significantly decreased by both doses of perindopril or the high dose of candesartan. Serum levels of angiotensin II and aldosterone were significantly higher in untreated Goldblatt rats. Both doses of perindopril inhibited activation of the renin-angiotensin system, whereas candesartan had weaker effects. In particular, serum aldosterone was 347 +/- 20 pg/ml in low-dose perindopril versus 1796 +/- 324 pg/ml in low-dose candesartan. These results suggest that there were no differences between the cardioprotective actions of perindopril and candesartan at high dosages. On the other hand, low-dose treatment with perindopril was more effective in preventing cardiac fibrosis than was low-dose treatment with candesartan, despite similar changes in blood pressure. It is possible that changes in aldosterone secretion are related to this difference.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan. mn3120@jikei.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Nagai
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Horikoshi
authors.forename: Takehiko
authors.initials: T
authors.lastname: Izumi
authors.forename: Shingo
authors.initials: S
authors.lastname: Seki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Ikuo
authors.initials: I
authors.lastname: Taniguchi
authors.forename: Seibu
authors.initials: S
authors.lastname: Mochizuki
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D006978:Hypertension, Renovascular / Q000517:prevention & control*; D008297:Male; D020913:Perindopril / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan; D020913:Perindopril