Cardiovascular, antihyperlipidemic and antioxidant effects of oleanolic and ursolic acids in experimental hypertension

Cardiovascular (systolic and diastolic blood pressure, heart rate), antihyperlipidemic (tryglycerides, total cholesterol and lipoprotein fractions), antioxidant (glutathione peroxidase - GPx, and superoxide dismutase - SOD), diuretic/saluretic and hypoglycemic activity of 98% pure oleanolic (OA) and ursolic (UA) acid were studied in Dahl salt-sensitive (DSS), insulin resistant rat model of genetic hypertension. Both OA and UA displayed low toxicity, with LC50 0.10 and 0.95 mg/ml, respectively. Although both triterpenoids did not have direct hypotensive effect, after 6-week application in a daily dose 60 mg/kg b.w., i.p., they prevented the development of severe hypertension. The antihypertensive effect was attributed to their potent diuretic-natriuretic-saluretic activity; direct cardiac effect (heart rate decrease by 34% and 32%, respectively); antihyperlipidemic (more than two times decrease of LDL and triglycerides); antioxidant (GPx increase by 12% and 10%, respectively; SOD increase by 12% and 22%, respectively), and hypoglycemic (blood glucose decrease by 20% and 50%, respectively) effects on the DSS rats. Except for the antihyperlipidemic effects, the other described above in vivo antihypertensive effects of OA and UA are reported for the first time and the underlying mechanisms are currently under investigation.