Enhancing hippocampal blood flow after cerebral ischemia and vasodilating basilar arteries: in vivo and in vitro neuroprotective effect of antihypertensive DDPH

Li Sun; Qin Li; Wei-Ting Wang; Yu-Hua Chen; Lian-Jun Guo

doi:10.4103/1673-5374.155432

Enhancing hippocampal blood flow after cerebral ischemia and vasodilating basilar arteries: in vivo and in vitro neuroprotective effect of antihypertensive DDPH

Neural Regen Res. 2015 Apr;10(4):589-93. doi: 10.4103/1673-5374.155432.

Authors

Li Sun¹, Qin Li², Wei-Ting Wang³, Yu-Hua Chen⁴, Lian-Jun Guo³

Affiliations

¹ 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.
² Department of Pharmacology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
³ Department of Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
⁴ Department of Neurology, Wuhan Brain Hospital (General Hospital of the Yangtze River Shipping), Wuhan, Hubei Province, China.

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.

Keywords: DDPH; NSFC grant; blood flow; cerebral ischemia; dose-response curve; hippocampus; isolated basilar artery; nerve regeneration; neural regeneration.