A specially prepared olive leaf extract (EFLA 943) has been tested for its blood pressure lowering activity in rats rendered hypertensive by daily oral doses of L-NAME (NG-nitro-L-arginine methyl ester, 50 mg/kg) for at least 4 weeks. Oral administration of the extract at different dose levels at the same time as L-NAME for a period of 8 weeks showed a dose dependent prophylactic effect against the rise in blood pressure induced by L-NAME, best effects being induced by a dose of 100 mg/kg of the extract. In rats previously rendered hypertensive by L-NAME for 6 weeks and then treated with that dose of the extract for a further 6 weeks without discontinuation of L-NAME, normalisation of the blood pressure was observed. The findings confirm previous reports on the hypotensive effects of olive leaf. The special extract, EFLA 943, was shown to give consistent results with little individual variability. The antihypertensive effect of the extract may be related to a variety of factors involving reversal of vascular changes involved in the L-NAME induced hypertension.

Accumulating evidence has indicated the implication of angiotensin II in the pathogenesis of inflammatory bowel diseases (IBD) via its proinflammatory features. Telmisartan (TLM) is an angiotensin II receptor antagonist with marked anti-inflammatory and antioxidant actions that mediated its cardio-, reno- and hepatoprotective actions. However, its impact on IBD has not been previously explored. Thus, we aimed to investigate the potential alleviating effects of TLM in tri-nitrobenezene sulphonic acid (TNBS)-induced colitis in rats. Pretreatment with TLM (10 mg/kg p.o.) attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI), colon weight/length ratio, macroscopic damage, histopathological findings and leukocyte migration. TLM suppressed the inflammatory response via attenuation of tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2) and myeloperoxidase (MPO) activity as a marker of neutrophil infiltration besides restoration of interleukin-10 (IL-10). TLM also suppressed mRNA and protein expression of nuclear factor kappa B (NF-κB) p65 and mRNA of cyclo-oxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proinflammatory genes with concomitant upregulation of PPAR-γ. The alleviation of TLM to colon injury was also associated with inhibition of oxidative stress as evidenced by suppression of lipid peroxides and nitric oxide (NO) besides boosting glutathione (GSH), total anti-oxidant capacity (TAC) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). With respect to apoptosis, TLM downregulated the increased mRNA, protein expression and activity of caspase-3. It also suppressed the elevation of cytochrome c and Bax mRNA besides the upregulation of Bcl-2. Together, these findings highlight evidences for the beneficial effects of TLM in IBD which are mediated through modulation of colonic inflammation, oxidative stress and apoptosis.

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The cellular mechanisms that underlie the enhancement of clonidine-evoked hypotension in aortic barodenervated (ABD) rats and its dependence on central adenosine A 2A receptor ( virtually abolished clonidine-evoked hypotension, clonidine-evoked enhancement of RVLM pERK1/2 production was only abrogated by SCH58261 pretreatment. These findings suggest that interventions that act centrally to increase RVLM neuronal pERK1/2 production elicit hypotension via the activation of downstream NOS-NO signaling. The findings also yield insight into a cellular mechanism that might explain the dependence of centrally (clonidine)-mediated hypotension on central A 2A R signaling in the ABD rat.Clonidine-evoked hypotension is enhanced in the aortic barodenervated (ABD) rat, which exhibits normal blood pressure compared with the sham-operated (SO) rat, despite a persistent baroreflex dysfunction and enhanced sympathetic tone (Osborn and England, 1990;Abdel-Rahman, 1992). The latter seems to contribute to the enhanced hypotensive response elicited by clonidine in ABD rats (Abdel-Rahman, 1992). Furthermore, in the same model, pharmacological blockade of central adenosine, and particularly the A 2A , receptor virtually abolished clonidine-evoked hypotension (Nassar and Abdel-Rahman, 2006a). These findings, which established a link between the molecular targets for clonidine, ␣ 2A R, and/or I 1 receptor, and central adenosine receptor signaling, are consistent with the physiological role of central A 2A R. It is noteworthy that in the RVLM, the major neuroanatomical target of clonidine, activation of the adenosine A 2A R causes hypotension (Thomas et al., 2000). However, the cellular mechanism implicated in the hypotension mediated by the activation of central adenosine A 2A R has not been investigated.In the RVLM, pERK1/2 is implicated in decreases or increases in blood pressure, depending on the experimental conditions and the preparation used (Seyedabadi et al., 2001;Springell et al., 2005;Zhang and Abdel-Rahman, 2005). In cell culture studies, A 2A R activation leads to This study was supported in part by National Institutes of Health Grant 2R01 AA07839.Article, publication date, and citation information can be found at http://jpet.aspetjournals.org. , intracisternal; L-NAME, N -nitro-L-arginine methyl ester; BP, blood pressure; HR, heart rate; aCSF, artificial cerebrospinal fluid; MAP, mean arterial pressure; ANOVA, analysis of variance; PD98059, 2Ј-amino-3Ј-methoxyflavone; ir, immunoreactive.