title: Effect of nilvadipine on the development of neurological deficits in stroke-prone spontaneously hypertensive rats.
abstract: OBJECTIVE
  Several types of antihypertensive drugs have been reported to protect stroke-prone spontaneously hypertensive rats from stroke. However, the clinical relevance remains unclear. This study was performed to investigate the effect of nilvadipine, a calcium channel blocker, on the development of neurological deficits in stroke-prone spontaneously hypertensive rats. In addition, plasma levels of nilvadipine were measured to determine the clinical relevance.
  
  
  METHODS
  Salt-loaded stroke-prone spontaneously hypertensive rats were orally administered nilvadipine mixed with a powder diet (0.01% and 0.03%, wt/wt). Non-salt-loaded rats were maintained on tap water. Chronological changes in neurological deficit scores and systolic blood pressure were recorded. After 6 weeks of medication, measurement of plasma levels of nilvadipine, serum biochemical analysis, and pathological observation of both the brain and the kidney were performed.
  
  
  RESULTS
  In the salt-loaded control group, both severe hypertension and neurological deficit developed, and the final survival rate was 30%. Systolic blood pressure decreased significantly in the high-dose nilvadipine-treated group but not in the low-dose nilvadipine-treated group. However, the development of neurological deficit was almost completely inhibited in both nilvadipine-treated groups that had no deaths (P < .01). The mean plasma levels of nilvadipine in the low-dose group and in the high-dose group at the time of death were 0.21 ng/mL and 0.61 ng/mL, respectively.
  
  
  CONCLUSIONS
  Nilvadipine inhibited the development of neurological deficit in stroke-prone spontaneously hypertensive rats at plasma concentrations lower than that in clinical use. Thus, nilvadipine might prevent cerebral vascular disorders at doses routinely used for essential hypertension.
authors.affiliation: Department of Pharmacology, Fujisawa Pharmaceutical Co, Ltd, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Takakura
authors.forename: Y
authors.initials: Y
authors.lastname: Furuichi
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Ogawa
authors.forename: H
authors.initials: H
authors.lastname: Satoh
authors.forename: J
authors.initials: J
authors.lastname: Mori
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000097:blood / Q000494:pharmacology*; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000517:prevention & control*; D004435:Eating / Q000502:physiology; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012965:Sodium Chloride / Q000097:blood; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; C035100:nilvadipine; D012965:Sodium Chloride; D009543:Nifedipine