Valsartan is a specific angiotensin II (AT!!)
antagonist acting at subtype I of AT receptors.
It has a dose dependent 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 blockade of
the vascular AT1
receptors subtype may also
contribute to its antihypertensive effect. This
study was designed to demonstrate the doseeffect
relationship of valsartan on MAP (mean
arterial pressure) of freely moving chronictIly
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 valsartan action on calcium or potassium
entry through their specific channels was also
explored. Infusion of valsartan (100 ug/kg/min)
for 10 min abolished the pressor effect of
ATI! in 4 doses of 1,3,10 and 30 ng/kg• and substantially
shifted noradrenaline dose-response
curves (10,30,100 and 300 ng/kg) to the right.
Valsartan bolus injecti.in in 4 successive doses
(10,30,100 and 300 ug/kg) produced dose dependent
reduction of MAP elevated and maintained
by AT, NA infusion or the nitric oxide synthase
inhibitor, NG-nitro-L-arginine methyl ester
CL-NAME; 10 mg/kg) injection. The presence of
indomethacin (1 mg/kg) potentiated and the presence
of verapamil (1 ug/kg) attenuated the
hypotensive effect of valsartan. In contrast,
glibenclamide Cl mg/kg) injection neither changed
L-NAME elevated MAP nor affected valsartan
hypotensive response. Thus, the hypotensive
effect of valsartan may involve Ca entry and
prostaglandins release but K and NO independent. |
