Cyclooxygertase-2 selective inhibitor,represent a new class of nonsteroldal
that exhibit preference for inhibition of cyclooxygenase-
2 (COX-2), the COX isoforrn thought to account largely for
prostaglandin(PG) formation in inflammation. COX-2 inhibitors have effective
antanflammatory action with reduced gastrointestinal toxicity relative
to classical NSAIDs which are widely used. Classical NSAIDs are associated
with adverse renal effects caused by reduction of renal PG
through inhibition of COX. Both isoforms of COX COX-1 & COX-2 are represented
in the kidney in constitutive and inducible forms.lt is assumed
therefore that the COX-2 inhibitors like celecoxib would have an effect on
renal function similar to that of classical NSAIDs. Also,it has been hypothesized
that COX-2 inhibitors may increase risk of cardio-vascular events
because of their inhibition of vascular prostacyclirt synthesis and lack of
an effect on platelet thromboxarte A2 production.
The present study was designed to study the effect of chronic administration
of COX-2 inhibitor, celecoxib, on blood pressure (BP) and renal
A function in normal rats in comparison with non-selective COX inhibitor, indomethacin.
Thus, changes in mean arterial blood pressure (MAP) during
treatment with celecoxib or indomethrtcin were detected, Also, changes in
renal blood flow (RBI) and serum Na, K. urea & creatinirte concentration
were all detected after 5 weeks treatment of rats with celecoxib or indomethacirt.
Moreover, as chronic treatment with nitric oxide synthetase inhibitor
(L-NAME) would cause increased dependance on vascular actions.
of prostacyclin. So, in this study, a model of L-NAME induced hypertension in rats was performed and the effect of celecoxib on BP of L-NAME
hypertensive rats was detected. Results from this study showed that five
weeks treatment of rats with celecoxib in a dose of 10 mg/ kg/day oral
caused a significant increase in MAP which started at end of second
week and progressively increased till end of fifth week and hypertensive
effect of celecoxib was more than that of indomethacin. Both celecoxib
and indomethacin caused significant elevation in serum K, urea and
creatinine but have no significant effect on serum Na. Indomethacin but
not celecoxib caused significant decrease in RBF. In L-NAME hypertensive
rats, chronic treatment of such rats with celecoxib in a dose of 10 mg/kg
oral daily produced significant elevation of BP in hypertensive rats compared
to group given vehicle. These results suggest that COX-2 inhibitors
affect vascular and renal functions causing increase in BP and decline in
renal function. Thus, COX-2 inhibitors should be used with caution since
they are like traditional NSAIDs can interfere with antituypertensive drugs
and can cause renal function impairment. |
