Gαq-RGS2 loop activator modulates the activity of vario us agonists on isolated heart and aorta of normal rats

The Gαq-RGS2 loop activator, 1-(5-chloro-2-hydroxyphenyl)-3-(4-(trifluoromethyl)-phenyl)-1H-1,2,4-triazol-5(4H)-one has demonstrated Gαq signaling inhibitor activity. Therefore, we aimed to study the effect of Gαq-RGS2 loop activator on isolated heart and aorta of normal rats. Heart and aorta were isolated from the sacrificed rats (n=6) and mounted on the langendroff's and organ bath assembly, respectively. The effect of various receptor-dependent (acetylcholine, angiotensin II and adrenaline) and independent (calcium chloride and sodium nitroprusside) agonists in absence and presence of Gαq-RGS2 loop activator on left ventricular systolic pressure (LVSP) and the contractile responseswere evaluated in isolated heart and aorta, respectively. Gαq-RGS2 loop activator (100 µM) significantly attenuated the adrenaline (p<0.001,) and angiotensin II (p<0.001) induced increase in LVSP in isolated heart and contractile response of adrenaline (p<0.01) and angiotensin II (p<0.01) in the aorta. However, effect calcium chloride did not significantly alter by Gαq-RGS2 loop activator. The effect of acetylcholinewas significantly (p<0.01, p<0.05) increased by Gαq-RGS2 loop activator in isolated heart and aorta. The effect of sodium nitroprusside significantly (p<0.01) potentiated by Gαq-RGS2 loop activator (100 µM) in isolated heart while it did not significantly alters in the aorta. Ultimately, the Gαq-RGS2 loop activator modulated the action of receptor-dependent agonists in isolated heart and aorta

Antiatherosclerotic activity of ibuprofen, a non-selective COX inhibitor--an animal study.

Atherosclerosis being considered as an inflammatory disorder, the present study was undertaken to investigate the effectiveness of anti-inflammatory drugs (ibuprofen, aspirin, and celecoxib) in hypercholesterolemia. Ibuprofen is a cyclooxygenase (COX-1 and COX-2) inhibitor known to reduce the production of prostaglandins that play prominent role in inflammation. Beside the anti-inflammatory effects that make ibuprofen interesting for the treatment of condition associated with hypercholesterolemic atherosclerosis. Various other properties of ibuprofen were investigated, ibuprofen showed better reduction in total cholesterol, triglycerides, very low density lipo-protein, low density lipo-protein and atherogenic index than aspirin and celecoxib in hypercholesterolemic animals. These properties of ibuprofen may be due to inhibition of acetyl-CoA carboxylase initiating the synthesis of fatty acids. Ibuprofen significantly elevated antioxidant (super oxide dismutase; catalase) levels and reduced lipid peroxidation. Ibuprofen inhibits COX enzymes and thereby inhibits generation of free radicals during prostaglandins synthesis, which may be responsible for reduction in lipid peroxidation, super oxide dismutase levels and for high catalase levels. Interestingly, ibuprofen decreased total leukocyte count, monocyte count, erythrocyte sedimentation rate and C-reactive protein levels. From the results of present study, it can be concluded that ibuprofen (non-selective COX inhibitor) showed promising antihyperlipidemic, antiatherosclerotic, antioxidant, antiinflammatory and non-ulcerogenic activity in atherosclerotic animals as compared to aspirin (preferential COX-1 inhibitor) and celecoxib (selective COX-2 inhibitors, suggesting the inducible role of COX in atherosclerosis.