Central Hypotensive Effects of Nicardipine in Conscious Freely Moving Spontaneously Hypertensive Rat

Abstract

The central cardiovascular effects of the calcium channel blocker nicardipine was studied in conscious freely moving normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Nicardipine was administered in a 1.5 μ1 volume into the lateral ventricle of the brain (i.c.v.) or intravenously (i.v.). The injection of vehicle alone did not significantly change mean arterial pressure (MAP) or heart rate (HR). Nicardipine (10,30,100 and 300 μg/kg), intravenously administered, dose-dependently decreased MAP and increased HR in WKY and SHR. However, when administered i.c.v., nicardipine (10 μg/kg) increased MAP and HR in WKY and decreased MAP without any significant change in HR in SHR. These results are consistent with previous work reporting an exaggerated hypotensive response to i.c.v. administration of dihydropyridine calcium channel blockers in anesthetized SHR as compared to WKY. They suggest that a 1,4–dihydropyridine-sensitive pressor system is present in the SHR but not in the WKY.

Key Words:

• 1,4—dihydropyridine
• calcium channel blocker
• spontaneously hypertensive rats
• central nervous system
• nicardipine