Candesartan is a specific angiotensin Ii (ATM antagonist at subtype
of AT receptors. It has a dose depended potent and long lasting blood
pressure lowering effect and is used as an effective once daily medication
for the treatment of hypertension. It has been suggested that mechanisms
other than blockn(1P of the vascular ATI- receptors subtype may also contribute
to its antihypertensive effect
This study was designed to demonstrate the dose-effect relationship
of candesartan on MAP (mean arterial pressure) offreely moving chronically
instrumented conscious rats. The involvement of the sympathetic nervous
system, the endothelium derived releasing factor (EDRF) known as nitric
oxide (NO) and prostaglandins in such effect was also investigated. The
dependence of candesartan action on calcium or potassium entry through
their specific channels was also explored. Infusion of candesartan (100
ug/kg/min) for JO min abolished the pressor effect of ATII in 4 doses of
1,3,10 and 30 mg/kg and substantially shifted noradrenaline dose-response
curves (10,30,100 and 300 ug/kg) produced dose dependent reduction of
MAP elevated and maintained by Al NA infusion or the nitric oxide syntheses
inhibitor, NG-nitro-L.arginine methyl ester (L-NAME; 10mg/kg) injection.
The presence of indomethacin (1 mg/kg) potentiated and the presence
of verapamil (1 ug/kg) attenuated the hypotensive effect of candesartan. In
contrast, glibenclatrzide (I mg/kg) injection neither changed L-NAME elevated
MAP nor affected candesartan hypotensive response Thus, the hypotensive
effect of candesartan may involve Ca entry and prostaglandins release but
K and NO independent |
