Ginkgo biloba extract [EGb761] normalizes hypertension in 2K, 1C hypertensive rats: roles of antioxidant mechanisms, ACE inhibiting activity and improvement of endothelial dysfunction

In the 2 kidney, 1-clip [2K, 1C] experimental renovascular hypertension, the early phase of elevation of blood pressure is associated with increase in plasma renin activity, and circulating angiotensin II which exerts a vasoconstrictor effect and increases aldosterone production. However, the progression and maintenance of the elevated blood pressure is mediated, in part, by angiotensin II-induced production of reactive oxygen species [ROS] which may promote endothelial dysfunction. The aim of the present study was to examine the possible antihypertensive effect of a standardized extract of Gingko biloba [EGb 761] in 2K,1C renal hypertensive rats and try to correlate it with the effect of the extract on oxidant status, ACE activity and vascular reactivity towards several vasoactive agents. Hypertension was induced using silver clip on renal artery by surgery. Four weeks after surgery, two sets of experiments were preformed. In the first set five groups of rats were selected; Sham-operated control, hypertensive control, and three hypertensive groups treated with the EGb 761 extract at 3 dose levels [60, 90, and 180 mg/kg/day; po] respectively for three weeks. Systolic blood pressure [SBP], heart rate [HR], lipid peroxidation measured as malondialdehyde [MDA], gIutathione peroxidase [GSH-Px] activity, nitric oxide [NO] level and angiotensin converting enzyme [ACE] activity were determined in blood, the ischemic kidney and the non-clipped contra-lateral kidney homogenates. In the second set of experiments three groups of animals were selected; Sham-operated control, hypertensive control, and hypertensive group treated with the EGb 761 [180 mg/kg/day; po] for three week after which the animals were sacrificed, the thoracic aortae isolated and prepared as rings for testing their reactivity towards the vasoactive agents norepinephrine [NE], acetyicholine [Ach], and sodium nitroprusside [SNP]. Results showed that clipping of the renal artery significantly elevated the SBP which reaches a plateau after 4 weeks, without any significant change in the HR. 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 EGb for 3 weeks produced a dose-dependent reduction in the SBP of the hypertensive rats and succeeded to normalize it with the highest dose level [180 mg/kg/day]. This antihypertensive action was associated with recovery of GSHPx activity in the ischemic kidney, inhibition of ACE activity in both kidneys, reduction of elevated NO in the non-clipped kidney, decreased responsiveness to the vasoconstrictor NE and improvement of endothelial function as evidenced by restoration of endothelium-dependent vasorelaxation induced by Ach

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

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

Caffeine induced fetal neural tube defects in mice and its influence on valproate teratogenesis

The effect of caffeine on fetal neural tube development was investigated in mice. Various oral dose regimens of caffeine were administered on gestation day-8 [GD8], GD9 or both to pregnant NMRI mice and fetuses were then examined on GDl8. Administration of caffeine [50 and 100 mg/kg] once daily on GD8 and on GD9 produced a dose-related increase in the incidence of spina bifida occulta [8.1% and 13.9%, respectively]. Administration of caffeine [50 mg/kg] three times 6 h apart on GD9 produced a higher incidence of spina bifida occulta reaching 27%. Fetuses with exencephaly were not observed as a result of administration of caffeine using either dose regimens [except of an odd fetus in the low dose group of the first regimen] or when caffeine [100 mg/kg] was given as a single administration on GD8. The influence of caffeine on sodium valproate [VPA]-induced neural tube defects [NTDs] was also studied. The study concluded that oral administration of caffeine [50 and 100 mg/kg] once daily on GD8 and on GD9 induced fetal spina bifida occulta in mice but the incidence was higher when the drug was given at the low dose three times on GD9. Furthermore, caffeine did not seem to influence VPA-induced NTDs when given either on GD8 or on GD9

Influence of L-arginine and N power G-nitro-L-arginine methyl ester on bleomyin -induced pulmonary toxicity

The current study aimed to investigate the effect of oral supplementation with the nitric oxide [NO] precursor; namely, L- arginine [ARG] and the NO synthesis inhibitor; namely, NG-nitro-L- arginine methyl ester [L-NAME] on bleomycin [BLM]-induced pulmonary toxicity. BLM was administered i.p. at a dose of 15 mg/kg, three times a week, for a total period of four weeks to male Wistar rats. Treatment with either ARG [500 mg/kg/day] or L-NAME [100 mg/kg/day] was commenced with BLM and continued up to the end of the experiment. Appropriate controls were performed. The results of the study indicated that the lung toxicity exerted by chronic administration of BLM is alleviated by ARG, while exacerbated by L-NAME supplementation and could address a possible protective role of NO