Effect of nilvadipine on the development of neurological deficits in stroke-prone spontaneously hypertensive rats.

Abstract

BACKGROUND AND PURPOSE:

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: S Takakura, Y Furuichi, T Yamamoto, T Ogawa, H Satoh, J Mori
• Journal: Stroke (Stroke) Vol. 25 Issue 3 Pg. 677-82; discussion 682-3 (Mar 1994) ISSN: 0039-2499 [Print] United States
• PMID: 8128525 (Publication Type: Journal Article)

Chemical References

• Calcium Channel Blockers
• nilvadipine
• Sodium Chloride
• Nifedipine

Topics

• Animals
• Calcium Channel Blockers (blood, pharmacology)
• Cerebrovascular Disorders (etiology, prevention & control)
• Eating (physiology)
• Hypertension (complications, drug therapy)
• Male
• Nifedipine (analogs & derivatives, blood, pharmacology)
• Rats
• Rats, Inbred SHR
• Sodium Chloride (blood)
• Time Factors