title: Enhancing hippocampal blood flow after cerebral ischemia and vasodilating basilar arteries: in vivo and in vitro neuroprotective effect of antihypertensive DDPH.
abstract: 1-(2,6-Dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)-propane hydrochloride (DDPH) is a novel antihypertensive agent based on structural characteristics of mexiletine and verapamine. We investigated the effect of DDPH on vasodilatation and neuroprotection in a rat model of cerebral ischemia in vivo, and a rabbit model of isolated basilar arteries in vitro. Our results show that DDPH (10 mg/kg) significantly increased hippocampal blood flow in vivo in cerebral ischemic rats, and exerted dose-dependent relaxation of isolated basilar arteries contracted by histamine or KCl in the in vitro rabbit model. DDPH (3 × 10(-5) M) also inhibited histamine-stimulated extracellular calcium influx and intracellular calcium release. Our findings suggest that DDPH has a vasodilative effect both in vivo and in vitro, which mediates a neuroprotective effect on ischemic nerve tissue.
authors.affiliation: Department of Neurology, Wuhan Brain Hospital (General Hospital of the Yangtze River Shipping), Wuhan, Hubei Province, China ; Department of Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Wang
authors.affiliation: Department of Neurology, Wuhan Brain Hospital (General Hospital of the Yangtze River Shipping), Wuhan, Hubei Province, China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Lian-Jun
authors.initials: LJ
authors.lastname: Guo
keywords: DDPH; NSFC grant; blood flow; cerebral ischemia; dose-response curve; hippocampus; isolated basilar artery; nerve regeneration; neural regeneration