TY - JOUR
T1 - Four-week administration of nimesulide, a cyclooxygenase-2 inhibitor, improves endothelial dysfunction in the hindlimb vasculature of streptozotocin-induced diabetic rats
AU - Abdelrahman, Aly M.
AU - Al Suleimani, Yousuf M.
N1 - Funding Information:
This work is supported by a grant from Sultan Qaboos University. We wish to thank Mr. Sultan Al Maskari and Mr. Sayed Fahrooq at the Small Animal House for their help.
PY - 2008/12
Y1 - 2008/12
N2 - The aim of this study was to examine the effect of chronic administration of nimesulide, a cyclooxygenase-2 inhibitor, on endothelial dysfunction in streptozotocin-induced diabetic rats. Three groups of Sprague-Dawley rats (300-350 g, n = 6) were used. The first group served as normoglycemic control and the second and third groups were rendered diabetic by an intraperitoneal injection of streptozotocin (60 mg/kg). The third group received the selective COX-2 inhibitor, nimesulide (20 mg/kg/day), orally by gavage for 4 weeks while the second group received only drinking water and served as diabetic control. At the end of the treatment period, the rats were anesthetized with urethane (1.2 g/kg) and mean arterial pressure, heart rate and hindlimb blood flow were monitored. This was followed by the injection of acetylcholine (endothelium-dependent vasodilator, 0.1-0.8 μg/kg) and sodium nitroprusside (endothelium-independent vasodilator 1-4 μg/kg). Mean arterial pressure was significantly reduced and hindlimb vascular conductance was not significantly affected in the control diabetic group when compared to the normoglycemic control group. Nimesulide treatment did not cause any significant change in any of the measured hemodynamic parameters. Acetylcholine and sodium nitroprusside induced dose-dependent increases in hindlimb vascular conductance in control normoglycemic rats which were attenuated in diabetic control rats. Nimesulide reversed the attenuation of acetylcholine-induced increase in hindlimb vascular conductance. In conclusion, chronic administration of the selective COX-2 inhibitor, nimesulide improved endothelial dysfunction in the hindlimb vasculature of streptozotocin induced diabetic rats. This suggests that COX-2 products might be involved in the pathogenesis of endothelial dysfunction in streptozotocin-induced diabetic rats.
AB - The aim of this study was to examine the effect of chronic administration of nimesulide, a cyclooxygenase-2 inhibitor, on endothelial dysfunction in streptozotocin-induced diabetic rats. Three groups of Sprague-Dawley rats (300-350 g, n = 6) were used. The first group served as normoglycemic control and the second and third groups were rendered diabetic by an intraperitoneal injection of streptozotocin (60 mg/kg). The third group received the selective COX-2 inhibitor, nimesulide (20 mg/kg/day), orally by gavage for 4 weeks while the second group received only drinking water and served as diabetic control. At the end of the treatment period, the rats were anesthetized with urethane (1.2 g/kg) and mean arterial pressure, heart rate and hindlimb blood flow were monitored. This was followed by the injection of acetylcholine (endothelium-dependent vasodilator, 0.1-0.8 μg/kg) and sodium nitroprusside (endothelium-independent vasodilator 1-4 μg/kg). Mean arterial pressure was significantly reduced and hindlimb vascular conductance was not significantly affected in the control diabetic group when compared to the normoglycemic control group. Nimesulide treatment did not cause any significant change in any of the measured hemodynamic parameters. Acetylcholine and sodium nitroprusside induced dose-dependent increases in hindlimb vascular conductance in control normoglycemic rats which were attenuated in diabetic control rats. Nimesulide reversed the attenuation of acetylcholine-induced increase in hindlimb vascular conductance. In conclusion, chronic administration of the selective COX-2 inhibitor, nimesulide improved endothelial dysfunction in the hindlimb vasculature of streptozotocin induced diabetic rats. This suggests that COX-2 products might be involved in the pathogenesis of endothelial dysfunction in streptozotocin-induced diabetic rats.
KW - Blood pressure
KW - COX-2 inhibitors
KW - Endothelium-dependent vasodilatation
KW - Nimesulide
KW - Streptozotocin-induced diabetic rats
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U2 - 10.1007/s12272-001-2155-5
DO - 10.1007/s12272-001-2155-5
M3 - Article
C2 - 19099228
AN - SCOPUS:58449099063
SN - 0253-6269
VL - 31
SP - 1584
EP - 1589
JO - Archives of Pharmacal Research
JF - Archives of Pharmacal Research
IS - 12
ER -