Experiments were performed on male and female spontaneously hypertensive rats weighing 310-340 g (10 animals per group). The oral administration of 200 mg/kg/day of saponins from Herniaria glabra for 30 days, resulted in a significant decrease in blood pressure in hypertensive rats. The systolic and diastolic blood pressure decreased significantly and respectively from 187.60 +/- 20.63/119.00 +/- 7.09 mmHg at day 0 (D0) to 141.60 +/- 7.51/90.40 +/- 7.68 mmHg at day 30 (D30), p < 0.001 (vs. 186.30 +/- 11.27/114.10 +/- 12.00 mm Hg at D0 to 154.50 +/- 6.38/132.3 +/- 7.68 mmHg at D30 in furosemide-treated group, p < 0.001). Control animals receiving placebo did not show any significant variation in the mean arterial pressure. The effect of saponins of Herniaria glabra on renal function was evaluated in spontaneously hypertensive rats using clearance techniques. Glomerular filtration rate was constant in the control rats and increased significantly in the hypertensive rats after saponins treatment (5.55 +/- 0.32 vs. 6.03 +/- 0.43 ml.min-1.kg-1 in the control (C) and saponins (S) groups, respectively, p < 0.05). Saponins administration provoked an increase in urinary flow (59.38 +/- 5.85 ml.kg-1.24 h-1 vs. 36.92 +/- 5.17 ml.kg-1.24 h-1, p < 0.001). Saponins also increased potassium excretion (6.89 +/- 0.81 mmol.kg-1.24 h-1 vs. 5.40 +/- 0.51 mmol.kg-1.24 h-1, p < 0.001) and sodium excretion (10.74 +/- 1.21 mmol.kg-1.24 h-1 vs. 7.25 +/- 0.54 mmol.kg-1.24 h-1, p < 0.001) as well as chloride excretion (13.59 +/- 1.04 mmol. kg-1.24 h-1 vs. 9.67 +/- 0.77 mmol.kg-1.24 h-1, p < 0.001). It is concluded that chronic oral administration of saponins from Herniaria glabra decreased the arterial blood pressure and affected salt and water transport in renal tubules.

Peganum harmala is plant known since the first century A.D. and still, currently used for therapeutic purposes. Harmaline, the active principle of the plant seeds, and its derivatives, cause visual troubles, loss of coordination, agitation and delirium, and, at high doses, it can produce paralysis. The present study was initiated to evaluate the use and manipulation of therapeutic doses of aqueous extract of P. harmala. Wistar rats were orally dosed acutely and the LD(50) obtained was 2.70+/-0.05g/kg. In chronic studies aqueous extract of P. harmala administered orally for six times a week at doses of 1, 1.35 and 2g/kg during 3 month period increased transaminases. Changes in glucose and creatinine were not significant. No significant gross changes were found at necropsy. Histologic study showed liver degeneration and spongiform changes in the central nervous system (CNS) in rats treated with 2g/kg dose but not at the therapeutic dose of 1g/kg.

The alkaloidic fraction of the methanol extract of Peganum harmala seeds was tested in vitro on three tumoral cell-lines: UCP-Med and Med-mek carcinoma, and UCP-Med sarcoma. Proliferation was significantly reduced at all tested concentrations (20-120 micrograms/ml) during the first 24 h of contact. A cell lysis effect occurred after 24 h and increased thereafter to complete cell death within 48-72 h, depending on tested concentration.

From ancient times, Peganum harmala was claimed to be an important medicinal plant. Its seeds were known to possess hypothermic, and essentially hallucinogenic properties. Various authors have undertaken studies on the antibacterial, antifungal and antiviral effects of Peganum harmala seeds, but studies on the antitumour activity are not to be found in the literature. In Moroccan traditional medicine, seed powder is sometimes used on skin and subcutaneous tumours. This work was designed to investigate some aspects of the antineoplastic properties of the plant Peganum. Varying concentrations (10 to 120 micrograms/ml) of total alkaloid extracts of Peganum harmala seeds (collected in Morocco) were tested in vitro on four tumoural cell-lines: Med-mek and UCP-Med carcinoma, UCP-Med sarcoma and Sp2/O-Ag14. In vivo experiments were performed with the Sp2/O cell-line grafted subcutaneously in syngenic BALB/c mice. In vitro, proliferation of tumoural cell lines was significantly reduced by all tested concentrations of the Peganum alkaloid extracts during the first 24 h of contact. A cell lysis effect occurred after 24 h and progressed to complete cell death within 48 to 72 h depending on the alkaloid concentration. Results obtained indicate that alkaloids of Peganum have a high cell toxicity in vitro. The active principle at a dose of 50 mg/kg given orally to mice for 40 days was found to have significant antitumoural activity. Peganum harmala alkaloids thus possess significant antitumour potential, which could prove useful as a novel anticancer therapy.

Nigella sativa (ranunculaceae) is used in Arab folk medicine as a diuretic and hypotensive plant. We report here the diuretic and hypotensive effects of dichloromethane extract of Nigella sativa seeds in the spontaneously hypertensive rat (SHR). An oral dose of Nigella sativa extract (0.6 ml/kg/day) and furosemide (5 mg/kg/day) increased significantly the diuresis by 16 and 30 per cent respectively after 15 days of treatment; urinary excretion of Cl-, Na+, K+ and urea is also increased. Simultaneously, the mean arterial pressure decreased respectively by 22 and 18 per cent in the Nigella sativa treated rat and nifédipine treated rat (0.5 mg/kg/day). In conclusion, the diuretic activity observed in the SHR rat treated with Nigella sativa seeds may be partially responsible for its diuretic action; it seems that other pathways may also be involved in their cardiovascular effects.

PURPOSE: In this study, we analyzed the consumption trends of antihypertensives in Morocco during the 1991-2010 period and the impacts after the institution of Mandatory Health Insurance and the marketing of generic drugs. METHODS: We used sales data from the Moroccan subsidiary of IMS Health "Intercontinental Marketing Service". The consumption volumes were converted into defined daily doses (DDDs). RESULTS: Between 1991 and 2010, outpatient consumption of antihypertensives went from 4.37 to 23.14 DDD/1000 inhabitants/day, a 5.30-fold increase. In 2010, calcium channel blockers (CCBs) and angiotensin converting enzyme inhibitors (ACEI) were the most consumed (4.97 DDD/1000 inhabitants/day) for each one, followed by diuretics (4.20 DDD/1000 inhabitants/day). The most consumed products were amlodipine (4.27 DDD/1000 inhabitants/day) followed by ramipril (3.18 DDD/1000 inhabitants /day) and indapamide (1.72 DDD/1000inhabitants/day). Between 1991 and 2010, the consumption of generic antihypertensives went from 2% to 46%. CONCLUSION: Antihypertensive consumption increased between 1991 and 2010. However, despite the increase of generic drugs consumption, the levels of antihypertensive consumption remain lower than the needs of hypertensive patients. Copyright © 2012 John Wiley & Sons, Ltd.

The acute toxicity study and the psychotropic activity of three alkylated derivatives of 3-(ethoxycarbonylmethylene)-2-oxo quinoxaline did not demonstrate any toxicity of these products at therapeutic dosages. In the animal, these compounds have sedative, myorelaxant and anxiolytic properities.

We investigated the toxicity of the fixed oil of Nigella sativa L seeds in mice and rats through determination of LD50 values and examination of possible biochemical, hematological and histopathological changes. The acute toxicity of Nigella sativa fixed oil was investigated in mice. LD50 values, obtained by single doses, orally and intraperitoneally administered in mice, were 28.8 ml/kg body wt. p.o.[26.2-31.6] and 2.06 ml/kg body wt. i.p.[1.86-2.26], respectively. Chronic toxicity was studied in rats treated daily with an oral dose of 2 ml/kg body wt. for 12 weeks. Changes in key hepatic enzymes levels, including aspartate-aminotransferase, alanine-aminotranferase, and gamma-glutamyltransferase and histopathological modifications (heart, liver, kidneys and pancreas) were not observed in rats treated with Nigella sativa after 12 weeks of treatment. The serum cholesterol, triglyceride and glucose levels and the count of leukocytes and platelets decreased significantly, compared to control values, while hematocrit and hemoglobin levels increased significantly. A slowing of body weight gain was also observed in Nigella sativa treated rats, as compared to control animals. The low toxicity of Nigella sativa fixed oil, evidenced by high LD50 values, key hepatic enzyme stability and organ integrity, suggests a wide margin of safety for therapeutic doses of Nigella sativa fixed oil, but the changes in hemoglobin metabolism and the fall in leukocyte and platelet count must be taken into consideration.

We investigated the effects of the fixed oil of Nigella sativa seeds in rats by monitoring blood homeostasis and body weight as well as toxicity. Animals were treated daily with an oral dose of 1 ml/kg body weight of the N. sativa seed fixed oil for 12 weeks. Changes in key hepatic enzymes levels were not observed in N. sativa treated rats after 12 weeks of treatment. The serum cholesterol, triglycerides and glucose levels and the count of leukocytes and platelets decreased significantly by 15.5, 22, 16.5, 35 and 32%, compared to control values, respectively; while haematocrit and haemoglobin levels increased significantly by 6.4 and 17.4%, respectively. In parallel, significant slowdown of the body weight evolution was observed in N. sativa treated animals comparatively to the animal control group. On the other hand, no mortality was noted for ten times the therapeutic dose in mice, during 15 days period after the oil administration (10 ml/kg p.o.). These results support the traditional use of N. sativa seeds as a treatment of the dyslipidemia and the hyperglycaemia, and related abnormalities; however, indicate a relative toxicity of this plant. Acute and chronic toxicity, and the mode of the action of the N. sativa fixed oil must be studied.

We studied the synthesis and psychotropic activity of the 7-phenyl-1,4-diazepin-5-one and derivatives. It can be conclude that these products have sedative, myorelaxant and anxiolytic actions. The toxicity study demonstrated that two diazepines are non-toxic at therapeutic dosages but that a third compound is very toxic.

PURPOSE The effects of partial nephrectomy (PN) on postoperative blood pressure (BP) are not known, and PN has the potential to worsen BP. We therefore sought to determine whether PN alters postoperative BP. MATERIALS AND METHODS Patients who underwent PN for suspected malignancy at our institution from 2002 to 2008 were included. Data on BP and medication from before and after PN were retrieved from family physicians. BP and number of antihypertensive medications were compared after surgery with preoperative values by use of paired t tests and Chi-squared analyses, respectively. RESULTS Of 74 patients undergoing PN and providing consent, 48 met the inclusion and exclusion criteria, with a median follow-up of 24 months. For the early postoperative period (1 month to 1 year after surgery), the mean BPs (132.3/77.0 mmHg) were unchanged compared with preoperative values (132.4/78.0 mmHg; p=0.59 systolic BP and p=0.30 diastolic BP). For the later postoperative period (beyond 1 year after surgery), the mean postoperative systolic BP was unchanged from the mean preoperative systolic BP (131.2 mmHg vs. 132.4 mmHg, respectively; p>0.30). However, the corresponding average diastolic BP was lower in the long term (78.0 mmHg versus 76.4 mmHg respectively; p=0.01). No significant difference in the mean number of BP medications prescribed preoperatively, at one year, and beyond one year was identified (p>0.37). CONCLUSIONS PN does not result in initial or long-term postoperative deterioration in BP.

ETHNOPHARMACOLOGICAL RELEVANCE Tulbaghia violacea Harv.(Alliaceae) is a small bulbous herb which belongs to the family Alliaceae, most commonly associated with onions and garlic. In South Africa, this herb has been traditionally used in the treatment of various ailments, including fever, colds, asthma, paralysis, hypertension and stomach problems. The aim of this study was to evaluate the effect of methanol leaf extracts (MLE) of Tulbaghia violacea on the blood pressure (BP) and heart rate (HR) in anaesthetized male spontaneously hypertensive rats; and to find out the mechanism(s) by which it acts. MATERIALS AND METHODS The MLE of Tulbaghia violacea (5-150mg/kg), angiotensin I human acetate salt hydrate (ang I, 3.1-100μg/kg), angiotensin II human (ang II, 3.1-50μg/kg), phenylephrine hydrochloride (phenylephrine, 0.01-0.16mg/kg) and dobutamine hydrochloride (dobutamine, 0.2-10.0μg/kg) were infused intravenously, while the BP and HR were measured via a pressure transducer connecting the femoral artery and the Powerlab. RESULTS Tulbaghia violacea significantly (p<0.01) reduced the systolic, diastolic, and mean arterial BP; and HR dose-dependently. Ang I, ang II, phenylephrine and dobutamine all increased the BP dose-dependently. The hypertensive effect of ang I and the HR-increasing effect of dobutamine were significantly (p<0.01) decreased by their co-infusion with Tulbaghia violacea (60mg/kg). However, the co-infusion of ang II or phenylephrine with Tulbaghia violacea (60mg/kg) did not produce any significant change in BP or HR when compared to the infusion of either agent alone in the same animal. CONCLUSIONS Tulbaghia violacea reduced BP and HR in the SHR. The reduction in BP may be due to actions of the MLE on the ang I converting enzyme (ACE) and β(1) adrenoceptors.

OBJECTIVES To describe the occurrence of systemic hypertension in dogs with acute kidney injury and the efficacy of amlodipine besylate for its treatment. METHODS This retrospective study included 52 dogs with acute kidney injury (2007 to 2008) grouped based on the use of amlodipine in their treatment. Systemic blood pressure was measured with an oscillometric device at admission, before, during, and after amlodipine therapy. RESULTS Occurrence of systolic systemic hypertension (≥160 mmHg) and severe systolic systemic hypertension (≥180 mmHg) was 37% and 15% at admission and increased with hospitalisation to 81% and 62%, respectively. Twenty-two dogs were treated with amlodipine, at a median daily dosage of 0·38 mg/kg (interquartile range 0·28 to 0·49) divided in one to two applications per day. Amlodipine therapy was associated with a decrease in systolic systemic blood pressure of 24 mmHg (12 to 34) and a correction of severe systemic hypertension in 10 of 11 dogs within 24 hours. Overall, 73% of the dogs survived with a significantly lower proportion of survivors in treated compared to non-treated dogs (59% versus 83%, respectively, P=0·05). CLINICAL SIGNIFICANCE Results of this study reveal that systemic hypertension is common in canine acute kidney injury and that treatment with amlodipine is beneficial in reducing systemic hypertension. The potential effect of amlodipine on global outcome requires prospective assessment.

Objective: In Poland and all over the world, whole-body cryostimulation is becoming more and more popular in the treatment of different diseases and in sport. However, changes that occur in the human body subjected to cryogenic temperatures are still not completely understood. Therefore, the aim of this study was to evaluate changes in blood circulation and aerobic capacity induced by repeated exposure to whole-body cryostimulation of young and clinically healthy male subjects. Material and Methods: The study included 25 young men, aged 21±0.9 years, average body weight 74.65±6.98 kg and height 179.5±5.12 cm. The participants were exposed to extremely low temperatures in a cryogenic chamber once a day for 15 days. Each session lasted 3 min at -130°C and was preceded by 30-second, adaptation in a vestibule at -60°C. Blood pressure and heart rate were measured before entering the chamber, immediately after exiting and 10 min later. We also calculated pulse pressure and the mean arterial blood pressure. Before and after the treatment the maximal oxygen uptake was measured. Results: Our results showed a significant increase in systolic blood pressure after each cryostimulation (by an average of 19 mmHg) and an increase in diastolic blood pressure only after the first cryostimulation (by 6 mm Hg). The increase in systolic blood pressure was accompanied by a significant decrease in heart rate (by about 7 bpm). No adaptation changes were observed after 15 treatments. There were no changes in aerobic capacity after 15 sessions of WBC, however we observed a significant decrease in RBC and hemoglobin concentration. Conclusion: Due to the increase in systolic blood pressure after WBC, this kind of physiotherapy treatment is not recommended for people with advanced or not pharmacologically controlled hypertension.

Powdered leaves (500 mg/kg body weight) of medicinal plants M. indica and C. igneus known to possess therapeutic effect were supplemented to streptozotocin induced diabetic rats. Leaf powders of both the plants were able to reduce blood glucose levels in the animals by 38 and 21% respectively after 15 days of supplementation. The preliminary results suggest that both the plants possess potent hypoglycemic activity.

Multiscale entropy (MSE) analysis provides information about complexity on various time scales. The aim of this study was to test whether MSE is able to detect autonomic dysregulation in young patients with diabetes mellitus (DM). We analyzed heart rate (HR) oscillations, systolic (SBP) and diastolic blood pressure (DBP) signals in 14 patients with DM type 1 and 14 age- and sex-matched healthy controls. SampEn values (scales 1-10) and linear measures were computed. HR: among the linear measures of heart rate variability significant differences between groups were only found for RMSSD (p = 0.043). MSE was significantly reduced on scales 2 and 3 in DM (p = 0.023 and 0.010, respectively). SBP and DBP: no significant differences were detected with linear measures. In contrast, MSE analysis revealed significantly lower SampEn values in DM on scale 3 (p = 0.039 for SBP; p = 0.015 for DBP). No significant correlations were found between MSE and linear measures. In conclusion, MSE analysis of HR, SBP and DBP oscillations is able to detect subtle abnormalities in cardiovascular control in young patients with DM and is independent of standard linear measures.

INTRODUCTION Antioxidants has been utilized to prevent oxidative damage in diabetes and hypertensive diseases. The current study evaluated the effect of alpha-tocopherol supplementation on blood pressure and the lipid profile in streptozotocin-induced diabetes mellitus in spontaneously hypertensive rats (SHR). METHODS The systolic blood pressure and total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were measured in SHR-diabetes induced. RESULTS Treatment with alpha-tocopherol (vitamin E) led to a decrease on systolic blood pressure and showed an increase of HDL-cholesterol and a decrease of LDL-cholesterol, but the concentrations of triglycerides and total cholesterol were not changed. CONCLUSIONS The vitamin E was able to modulate the blood pressure and the lipidic profile as well, and therefore can be considered as an alternative treatment of lipid disorder found on diabetes and hypertension diseases.

The application of high-dose immunoglobulins during xenoperfusion of the isolated rat heart resulted in a significantly higher pressure and heart rate. The coronary flow was also elevated as compared to untreated controls. The heart function during xenoperfusion without treatment was reduced to 50% of the baseline values within 11 min. With immunoglobulin treatment the occurrence of this deficit was delayed to 30 min. A concentrate of immunoglobulins was able to reduce the early functional damage of xenoperfused hearts by interfering with complement related graft destruction.

This study reports the effect of paraquat (PQ) on concentrations of four elements (Cu, Fe, Mg, Zn) in lung, kidney, spleen, liver, and heart of male osteogenic disorder Shionogi (ODS) rats, a strain not able to synthesize vitamin C. PQ significantly increased the Cu concentrations in lung, liver, and plasma, accompanied by a fall in renal levels. Fe levels were elevated in liver and spleen but lowered in plasma. PQ produced an increase in kidney Mg and a rise in liver Mg and Zn levels. Cardiac elemental levels were not affected by PQ treatment. PQ, a known oxidant, produced changes in tissue elements involved in antioxidant mechanisms.

Epidemiological studies suggest that n-3 polyunsaturated fatty acids (PUFA) are involved in the prevention of cardiovascular disease. Stress is known to increase the incidence of CVD and the present study was realised to evaluate some physiological and biochemical effects of dietary docosahexaenoic acid (DHA) in male Wistar rats subjected to a psycho social stress. Rats were fed for 8 weeks a semi-purified diet containing 10% of either sunflower seed oil or the same oil supplemented with DHA. This food supply represented 50% of their daily requirement. The remaining 50% were supplied as 45 mg food pellets designed to induce stress in rats by an intermittent-feeding schedule process. The control group (n = 12) was fed the equivalent food ration as a single daily feeding. The physiological cardiovascular parameters were recorded by telemetry through a transmitter introduced in the abdomen. At the end of the experimentation, the heart and adrenals were withdrawn and the fatty acid composition and the catecholamine store were determined. Dietary DHA induced a pronounced alteration of the fatty acid profile of cardiac phospholipids (PL). The level of all the n-6 PUFAs was reduced while 22:6 n-3 was increased. The stress induced a significant increase in heart rate which was not observed in DHA-fed group. The time evolution of the systolic blood pressure was not affected by the stress and was roughly similar in the stressed rats of either dietary group. Conversely, the systolic blood pressure decreased in the unstressed rats fed DHA. Similar data were obtained for the diastolic blood pressure. The beneficial effect of DHA was also observed on cardiac contractility, since the dP/dt(max) increase was prevented in the DHA-fed rats. The stress-induced modifications were associated with an increase in cardiac noradrenaline level which was not observed in DHA-fed rats. The fatty acid composition of adrenals was significantly related to the fatty acid intake particularly the neutral lipid fraction (NL) which incorporated a large amount of DHA. Conversely, n-3 PUFAs were poorly incorporated in adrenal phospholipids. Moreover the NL/PL ratio was significantly increased in the DHA fed rats. The amount of adrenal catecholamines did not differ significantly between the groups. These results show that a supplementation of the diet with DHA induced cardiovascular alterations which could be detected in conscious animals within a few weeks. These alterations were elicited by a reduced heart rate and systolic and diastolic blood pressure.