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薬理と治療
Abstract
Objective To clarify pharmacological properties of a novel angiotensinⅡ type 1 receptor blocker(ARB), azilsartan, we conducted several in vivo experiments using normal rats,hypertensive rats and dogs and type 2 diabetic rats exhibiting overt albuminuria.Methods We first evaluated in vivo antagonistic activities of orally administered azilsartan and launched ARBs, olmesartan medoxomil(O. M.)and candesartan cilexetil(C. C.)in normotensive rats. Second, we clarified antihypertensive effects of single or repeated administrations of these ARBs in spontaneously hypertensive rats (SHR), a model of essential hypertension. We also confirmed the antihypertensive effect of azilsartan in renal hypertensive dogs. In addition, we studied the insulin-sensitizing effect and the anti-albuminuria effect of azilsartan using SHR and Zucker diabetic fatty(ZDF)rats which exhibiting overt albuminuria,respectively. We also compared the effects of azilsartan with those of O. M. or C. C. Results Azilsartan inhibited angiotensinⅡ -induced pressor responses in normotensive rats, and its inhibitory effect is longer-lasting than those of O. M. and C. C. In SHRs, azilsartan reduced blood pressure more potently than O. M. and more persistently than O. M. and C.C. In renal hypertensive dogs, single oral administration of azilsartan at 0.3-3 mg/kg reduced BP, and it reduced even 24 hours after administration at 3 mg/kg. In a 2-week repeat dosing study in SHRs, azilsartan showed a more stable antihypertensive effect than O. M., and it more potently improved the glucose infusion rate, an indicator of insulin sensitivity, than O. M. Azilsartan also exerted more potent antiproteinuric effects than C. C. in ZDF rats.Conclusion These results suggest that azilsartan is a potent ARB that has a favourable profile as an antihypertensive agent.
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