Study of the antihypertensive effect of olea europea extract [EFLA 943] in renal hypertensive rats: roles of ACE activity, redox state, and vascular liorepinephrine responsiveness

ABSTRACT

Standardized extract from leaves of Olea europea [EFLA 943] constitutes a mixture of biologically active natural products with a broad range of pharmacological activities. It has received a great deal of attention recently with respect to its cardiovascular effects. The present work has been undertaken to assess the possible potential antihypertensive effect of the extract and try to correlate it with its effect on oxidant status, ACE activity and vascular reactivity in the 2-kidney, 1-clip [2K, 1C] renal hypertensive rats. Two sets of experiments were performed. In the first set 3 groups of rats were selected; Sham-operated control, hypertensive control, and EFLA 943-trcated hypertensive groups. Hypertension was induced using silver clip on the renal artery by surgery. Four weeks after surgery, a single daily dose of 180 mg/kg/day; po of EFLA 943 was given for three weeks. Blood pressure was measured by the tail-cuff method weekly. ACE activity, malondialdehyde [MDA], glutathione peroxidase [GSHPx], total protein thiols [Pr-SHs], and nitric oxide [NO] were determined in the clipped kidney non-clipped kidney and blood. A second set of experiments with 3 groups and similar treatment like the first one was conducted but at the end of the treatment period rats were sacrificed, the thoracic aortae isolated and prepared as rings for testing their reactivity towards norepinephrine [NE], acetylcholine [Ach], and sodium nitroprusside [SNP]. Results showed that clipping of the renal artery significantly elevated the systolic blood pressure [SBP] which reaches a plateau after 4 weeks. MDA significantly increased in serum and the clipped kidney GSH-Px significantly decreased in the ischemic kidney while it was significantly elevated in serum and the contra-lateral kidney. NO level as well as ACE activity significantly increased in both kidneys without being affected in blood. There was impairment in both endothelium-dependent and independent relaxation of aortic rings towards Ach and SNP respectively. Treatment with EFLA 943 produced a significant reduction in the SBP of the hypertensive rats. This antihypertensive action was associated with inhibition of ACE activity in the non-clipped kidney, reduction of serum MDA, decrease in total Pr-SHs normalization of NO in both kidneys, and recovery of GSHPx activity in the ischemic kidney, together with decreased responsiveness to the vasoconstrictor NE