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(Hypertension. 2000;35:769.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Cardiovascular Effects of Combination of Perindopril, Candesartan, and Amlodipine in Hypertensive Rats

Shokei Kim; Yumei Zhan; Yasukatsu Izumi; Hiroshi Iwao

From the Department of Pharmacology, Osaka City University Medical School, Abeno-ku, Osaka, Japan.

Correspondence to Shokei Kim, MD, PhD, Department of Pharmacology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. E-mail kims{at}med.osaka-cu.ac.jp

Abstract—The combination therapy with ACE inhibitors, angiotensin II type 1 (AT₁) receptor antagonists, or calcium channel antagonists may exert more beneficial effects on cardiovascular diseases than monotherapy. Perindopril, candesartan cilexetil, or amlodipine alone or the combination of low doses of each agent was administered orally to stroke-prone spontaneously hypertensive rats (SHRSP) for 4 weeks to compare the hypotensive or cardiovascular effects. Although perindopril (2 mg/kg), candesartan cilexetil (2 mg/kg), or amlodipine (3 mg/kg) alone caused comparable hypotensive effects in SHRSP, monotherapy with perindopril or candesartan decreased left ventricular (LV) weight; mRNA levels for atrial natriuretic factor, skeletal -actin, and collagen types I and III; and aortic weight and platelet-derived growth factor-ß receptor tyrosine phosphorylation to a greater extent than monotherapy with amlodipine. Although monotherapy with a low dose (0.2 mg/kg) of perindopril or candesartan cilexetil did not significantly reduce the LV mRNA levels and aortic platelet-derived growth factor-ß receptor phosphorylation of the SHRSP, combination therapy at such a low dose normalized these parameters more potently than the use of amlodipine (3 mg/kg) alone. Although perindopril or candesartan cilexetil alone at 0.05 mg/kg did not decrease the blood pressure of the SHRSP, such a low dose of combination therapy decreased LV weight and atrial natriuretic factor mRNA levels of the SHRSP to a greater extent than amlodipine alone or amlodipine combined with perindopril or candesartan cilexetil. Our results provide evidence that suggests the combination of an ACE inhibitor and an AT₁ receptor antagonist may be more effective in the treatment of cardiac and vascular diseases than the combination of a calcium channel blocker with an ACE inhibitor or an AT₁ receptor antagonist or monotherapy with each agent.

Key Words: angiotensin • calcium • hypertrophy • platelet-derived growth factor • rats, stroke-prone SHR • antihypertensive therapy

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