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Persistent effect of treatment with candesartan cilexetil on blood pressure in spontaneously hypertensive rats

Department of Pharmacology, University of Aarhus, Aarhus, Denmark

Susie Mogensen

Department of Pharmacology, University of Aarhus, Aarhus, Denmark

Michael J Mulvany

Department of Pharmacology, University of Aarhus, Aarhus, Denmark, mm{at}farm.au.dk

We have investigated whether the angiotensin II type-1 (AT₁) receptor antagonist, candesartan cilexetil, has a persistent effect on blood pressure even after withdrawal of treatment, as has been shown consistently for angiotensin-converting enzyme inhibitors (ACE-1). Spontaneously hypertensive rats (SHR) were divided into four groups (n=16 per group) and treated with candesartan cilexetil (high-dose: 5 mg/kg/day; middle-dose: 1 mg/kg/day; low-dose: 0.5 mg/kg/day) or control from age four weeks to 20 weeks. Normotensive Wistar-Kyoto rats (WKY) were also investigated. The drug was given in the drinking water, the concentration adjusted for water consumption and rat weight. Blood pressure (BP) was measured regularly by the indirect tail-cuff method during the treatment period and after treatment, from age 20 weeks to 32 weeks.

At age 20 weeks, candesartan treatment had caused a slight reduction in body weight, an increase in water consumption and a reduction in heart rate. During treatment, candesartan caused a dose-dependent reduction in BP. After withdrawal of treatment, BP increased but remained lower than that of untreated control SHR for the medium- and high-dose groups throughout the follow-up period, the reduction being 8—11% at the end of follow-up. At age 32 weeks, there was no significant difference between the three candesartan-treated groups.

We conclude that treatment with the AT₁-receptor antagonist candesartan has a modest persistent effect on BP after withdrawal of treatment.

Key Words: persistent antihypertensive effect • spontaneously hypertensive rat • withdrawal of treatment

Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 1 suppl, S91-S94 (2001)
DOI: 10.1177/14703203010020011601


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