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Chronopharmacology of angiotensin II-receptor blockers in stroke-prone spontaneously hypertensive rats.

Abstract：

:Protective effect of valsartan (Val), an angiotensin II (AII)-receptor blocker (ARB), against organ damage is reported to depend on the dosing time in hypertensive patients. Dosing-time-dependent effect of Val on survival of stroke-prone spontaneously hypertensive rats (SHRSP) under a 12-h lighting cycle was examined. Val (4 mg/kg per day) and olmesartan medoxomil (OM) (1 mg/kg per day), another ARB with a slower dissociation from the AII receptor, were given once daily at 2, 8, 14, or 20 HALO (hours after lights on). Dosing-time-dependent differences in plasma drug concentrations and effect on blood pressure (BP) were also evaluated. Survival of SHRSP showed a dosing-time-dependent change during Val therapy, with a peak at 2 HALO and a trough at 14 HALO. OM equally prolonged survival in all groups. The BP-lowering effect persisted for more than 24 h after dosing of Val at 2 HALO and of OM at 2 and 14 HALO, but disappeared at 5.5-h after Val dosing at 14 HALO. Plasma concentrations of Val and OM were higher after dosing at 2 HALO than at 14 HALO. These results suggest that the chronopharmacological phenomenon of Val was partly due to the dosing-time-dependent difference in plasma concentration and subsequent duration of the antihypertensive effect. Slower dissociation of OM from AII receptors might have blunted a potential dosing-time-dependent event.

journal_name

J Pharmacol Sci

journal_title

Journal of pharmacological sciences

authors

Liu Y,Ushijima K,Ohmori M,Takada M,Tateishi M,Ando H,Fujimura A

doi

10.1254/jphs.10284fp

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

196-204

issue

2

eissn

1347-8613

issn

1347-8648

pii

JST.JSTAGE/jphs/10284FP

journal_volume

115

pub_type

杂志文章

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