The effect of civil and military flights on coagulation, fibrinolysis and blood flow: insight from a rat model.

BACKGROUND: Air travel thrombosis continues to be a controversial topic. Exposure to hypoxia and hypobaric conditions during air travel is assumed a risk factor. The aim of this study is to explore changes in parameters of coagulation, fibrinolysis and blood flow in a rat model of exposure to hypobaric conditions that imitate commercial and combat flights. METHODS: Sixty Sprague-Dawley male rats, aged 10 weeks, were divided into 5 groups according to the type and duration of exposure to hypobaric conditions. The exposure conditions were 609 m and 7620 m for 2 and 12 h duration. Blood count, thrombin- antithrombin complex, D-dimer, interleukin-1 and interleukin-6 were analyzed. All rats went through flight angiography MRI at day 13-post exposure. RESULTS: No effect of the various exposure conditions was observed on coagulation, fibrinolytic system, IL-1 or IL-6. MRI angiography showed blood flow reduction in lower limb to less than 30% in 50% of the rats. The reduction in blood flow was more pronounced in the left vessel than in the right vessel (p = 0.006, Wilcoxon signed rank test). The extent of occlusion differed across exposure groups in the right, but not the left vessel (p = 0.002, p = 0.150, respectively, Kruskal-Wallis test). However, these differences did not correlate with the exposure conditions. CONCLUSION: In the present rat model, no clear correlation between various hypobaric conditions and activation of coagulation was observed. The reduction in blood flow in the lower limb also occurred in the control group and was not related to the type of exposure.

Normal adiponectin levels in kidney transplant patients with hypertension.

BACKGROUND: Kidney transplant patients are a unique population where despite correction of their kidney function they are still considered to be at high cardiovascular (CV) risk. Adiponectin, an adipokine secreted from adipocytes, has protective CV properties. Patients with essential hypertension (HTN) have low adiponectin levels that are associated with a high CV risk. The aim of this study was to assess adiponectin levels in hypertensive renal transplant recipients. MATERIALS AND METHODS: Fasting blood adiponectin levels were measured in hypertensive kidney transplant patients (n = 18), patients with essential HTN (n = 17) and healthy subjects (n = 14). Patients with diabetes mellitus and renal failure were excluded from the study. Anthropomorphic and metabolic parameters were also measured. RESULTS: Patients with essential HTN had lower adiponectin levels than healthy controls (6 ± 0.7 µg/mL vs. 11 ± 0.9 µg/mL, p < 0.001), whereas hypertensive kidney transplant patients had adiponectin levels that were similar to adiponectin levels found in normal controls (11 ± 1.1 µg/mL). Adiponectin levels in healthy subjects were inversely correlated with plasma triglycerides (r = -0.876, p < 0.001) and with body weight (r = -0.7, p < 0.001). There was no such a correlation in patients with HTN. CONCLUSION: Adiponectin in hypertensive kidney transplant recipients is not an appropriate CV risk marker as it does not adequately distinguish these patients from normal controls.

Effects of allicin on cardiovascular risk factors in spontaneously hypertensive rats.

BACKGROUND: Allium sativum, the active ingredient in garlic, is known to have a beneficial effect on major cardiovascular risk factors, including dyslipidemia, blood pressure, blood glucose and insulin levels. However, the data on the significance of these effects are inconsistent due to methodological limitations, especially the use of whole garlic cloves which does not allow controlled dosing of the active compound. OBJECTIVES: To study the effects of purified allicin on the cardiovascular system. METHODS: Spontaneously hypertensive rats treated for 6 weeks with a daily dose of 80 mg/kg/day of purified allicin added to their chow were compared to control rats that were fed regular chow. Weight, systolic blood pressure (SBP), triglycerides, cholesterol, insulin and adiponectin were measured at baseline and at the end of the study. RESULTS: Allicin had no effect on body weight whereas it reduced SBP significantly from 190 +/- 7.5 mmHg to 168 +/- 5.7 (P < 0.0001) and triglyceride levels from 96 +/- 25 mg/dl to 71 +/- 19 (P = 0.009). Allicin had no effect on plasma cholesterol, insulin and adiponectin levels. CONCLUSIONS: Allicin lowered blood pressure and triglyceride levels in spontaneously hypertensive rats. This effect was not mediated through weight loss.

Ambient illuminance, retinal dopamine release and refractive development in chicks.

Form deprivation and low illuminance of ambient light are known to induce myopia in chicks. Low concentrations of retinal dopamine, a light-driven neurohormone, was previously shown to be associated with form deprivation myopia. In the present study we examined the dependence of retinal dopamine release in chicks on illuminance during light-dark cycles and in continuous light, and the role of retinal dopamine release in illuminance dependent refractive development. Newly hatched chicks (n = 166) were divided into two experimental groups, a dopamine (n = 88) and a refraction group (n = 78). Both groups were further divided into six illumination groups for exposure of chicks to illuminances of 50, 500 or 10,000 lux of incandescent illumination (referred to throughout as low, medium, and high illuminance, respectively), either under a light-dark cycle with lights on between 7 AM and 7 PM or under continuous illumination. For the dopamine experiment, chicks were euthanized and vitreous was extracted on day 14 post-hatching at 7, 8 AM and 1 PM. Vitreal dihydroxyphenylacetic acid (DOPAC) and dopamine concentrations were quantified by high-performance liquid chromatography coupled to electrochemical detection. For the refraction experiment, chicks underwent refraction, keratometry and A-scan ultrasonography on days 30, 60 and 90 post-hatching, and each of those measurements was correlated with vitreal DOPAC concentration measured at 1 PM (representing the index of retinal dopamine release). The results showed that under light-dark cycles, vitreal DOPAC concentration was strongly correlated with log illuminance, and was significantly correlated with the developing refraction, corneal radius of curvature, and axial length values. On day 90, low vitreal DOPAC concentrations were associated with myopia (-2.41 ± 1.23 D), flat cornea, deep anterior and vitreous chambers, and thin lens. Under continuous light, vitreal DOPAC concentrations measured at 1 PM in the low, medium, and high illuminance groups did not differ from the concentrations measured at 8 AM. On day 90, low DOPAC concentrations were associated with emmetropia (+0.63 ± 3.61), steep cornea, and shallow vitreous chamber. We concluded that ambient light over a log illuminance range of 1.69-4 is linearly related to vitreal DOPAC concentration. Under both light-dark cycles and continuous light, the intensity of ambient light regulates the release of retinal dopamine. Refractive development is associated with illuminance dependent dopamine release.

The role of melatonin in the pathogenesis of hypertension in rats with metabolic syndrome.

BACKGROUND: Melatonin, the primary hormone of the pineal gland, is a known modulator of various physiological processes. The aim of this study was to evaluate the role of melatonin in the pathogenesis of hypertension in rats with metabolic syndrome and to assess whether melatonin supplementation prevents the development of hypertension in this model. METHODS: Twenty male Sprague-Dawley (SD) rats were fed either a high fructose diet (n = 10) or a regular diet (control; n = 10) for 5 weeks. Urinary excretion of 6-hydroxymelatoninsulfate (a metabolite of melatonin) was measured at the beginning and the end of the study. An additional 20 SD rats were fed with the same diets but with a supplementation of melatonin (30 mg/kg/day) in their drinking water. Blood pressure (BP) was measured every week. RESULTS: BP increased significantly in rats fed with a high fructose diet and remained unchanged in the control group. The BP rise was associated with a significant decrease in melatonin secretion during sleep. Melatonin supplementation prevented the BP rise in fructose fed rats. BP increased by 14.6 +/- 1.0 mm Hg in the fructose fed rats, whereas it increased by only 3 +/- 2.6 mm Hg in rats fed with fructose and melatonin (P < 0.001 between groups). CONCLUSIONS: Melatonin secretion decreased in fructose fed rats that developed hypertension. Administration of melatonin blunted this BP rise. These data suggested that melatonin plays a role in the pathogenesis of hypertension in rats with metabolic syndrome.

Metabolic syndrome: comparison of the two commonly used animal models.

BACKGROUND: The etiology of the metabolic syndrome (MS) includes both genetic and environmental factors. The two most commonly studied animal models of the MS are the high-sucrose diet given to spontaneously hypertensive rats (SHRs) and high-fructose diet given to Sprague Dawley rats (SDRs). This study compares between these two models. METHODS: The two rat strains were examined; within each group, the rats were assigned to either the high-sugar diet (SDRs with fructose-enriched diet and SHRs with sucrose-enriched diet) or standard rat chow (control group). The rats were followed for 7 weeks. The main MS components (obesity, hypertension, impaired glucose tolerance, hyperinsulinemia, hypertriglyceridemia, and hypercholesterolemia) were measured. RESULTS: At baseline systolic blood pressure (SBP), fasting blood levels of triglycerides and insulin, as well as glucose intolerance, were significantly higher among the SHRs compared to SDRs. Following fructose enrichment, SDRs became hyperinsulinemic, hypertriglyceridemic, hypercholesterolemic, hypertensive, and insulin resistant, whereas SHRs responded to sucrose supplementation by a significant elevation in blood pressure and mild worsening of insulin resistance. Endpoint results revealed superiority of sucrose--SHR model in terms of hypertension and superiority of fructose--SDR model in terms of hyperinsulinemia, hypertriglyceridemia, and hypercholesterolemia. Both models showed similar postintervention degree of glucose tolerance. CONCLUSIONS: The fructose-fed SDR model represents a predominantly environmentally acquired MS, whereas the SHR model is less affected by dietary intervention and better displays the predominantly genetic spontaneous appearance of the syndrome. This fundamental difference should be taken into consideration when choosing an animal model to study the MS.

Effect of telmisartan, angiotensin II receptor antagonist, on metabolic profile in fructose-induced hypertensive, hyperinsulinemic, hyperlipidemic rats.

The metabolic syndrome (MS) is a common risk factor for cardiovascular disease and type-2 diabetes. Recently, telmisartan, an angiotensin II receptor antagonist that has an antihypertensive effect, has been reported to be a partial peroxisome proliferator-activated receptor gamma (PPARgamma) agonist. The anti-diabetic hormone adiponectin has been recognized as a marker of in vivo PPARgamma activation. Therefore, we studied telmisartan's effect on the metabolic profile and adiponectin levels in a fructose-induced hypertensive, hyperinsulinemic, hyperlipidemic rat model. Twenty-four male Sprague-Dawley rats were divided into three groups (eight in each). One group of control rats was fed standard chow for 5 weeks while a second was fed a fructose-enriched diet. A third group was fed a fructose-enriched diet for 5 weeks and treated with telmisartan 5 mg/kg/day during the last 2 weeks. Fructose feeding increased systolic blood pressure (mean+/-SEM), from 130+/-1 to 148+/-2 mmHg, insulin from 0.26+/-0.03 to 0.68+/-0.08 ng/mL, and triglycerides from 102+/-6 to 285+/-23 mg/dL (p<0.05 for all variables). Telmisartan treatment reversed these effects and reduced blood pressure to 125+/-2 mmHg, insulin levels to 0.41+/-0.07 ng/mL, and triglycerides to 146+/-18 mg/dL (p<0.05 for all variables), while attenuating the increase in body weight during weeks 3 to 5. In contrast, telmisartan did not affect plasma adiponectin levels. In conclusion, although telmisartan is considered a partial PPARgamma agonist, its beneficial effect in the fructose-induced hypertension, hypertriglyceridemia, and hyperinsulinemia rat model is apparently not mediated by adiponectin elevation but rather by direct inhibition of AT1 receptor.

Saccharin Increases Fasting Blood Glucose but Not Liver Insulin Resistance in Comparison to a High Fructose-Fed Rat Model.

Recent data indicate that artificial sweeteners (AS) may have deleterious effects on glucose metabolism. The purpose of this study was to compare the effects of AS and the effects of a high fructose diet (HFrD) on glucose metabolism and insulin resistance (IR) in Sprague-Dawley (SD) rats. SD rats were fed either regular chow, chow with saccharin (Sac) (0.1 mg/mL) placed in their water, or HFrD for seven weeks. Glucose, insulin, and triglycerides (Tg) levels were measured upon completion. A homeostatic model assessment (HOMA)-IR index was used to determine insulin resistance. The liver was stained to detect signs of a fatty liver. Hepatic mRNA expression of glucose metabolism regulation genes, Srepb-1c (sterol regulatory element binding protein) and ChREB (α & ß) (carbohydrate response element binding protein), as well as other glycolytic and lipogenic genes including glucose-6-phosphatase (G6pc), were considered IR markers. Both HFrD and Sac significantly increased fasting blood glucose levels compare to the control (140 ± 5 and 137 ± 6 vs. 118 ± 3 mg/dL, respectively, p < 0.05). However, only HFrD increased insulin secretion (0.99 ± 0.12 vs. 0.7 ± 0.1 and 0.6 ± 0.1 ug/L), Tg levels (420 ± 43 vs. 152 ± 20 and 127 ± 13 mg/dL), and the HOMA-IR index (3.4 ± 0.4 vs. 2.3 ± 0.36 and 2.13 ± 0.3) (HFrD vs. control and sac, p < 0.05). Fatty liver changes were only observed in HFrD fed rats. The expression of ChREB ß, Srepb-1c, and G6pc mRNA were only significantly elevated (between 2-10 times folds, p < 0.05) in HFrD fed rats. Sac may increase fasting blood glucose but has no effect on liver insulin resistance.

Effect of PPAR-gamma agonist on adiponectin levels in the metabolic syndrome: lessons from the high fructose fed rat model.

BACKGROUND: The health hazard of the metabolic syndrome (MS) is increasing, yet there is no effective pharmacologic treatment to this entity as a whole. Recently, hypoadiponectinemia was found to play an important role in the development of MS. We studied the effect of the PPAR-gamma agonist rosiglitazone on adiponectin and the metabolic profile in the fructose-induced hypertensive, hyperinsulinemic, hypertriglyceridemic rat model. METHODS: Thirty male Sprague-Dawley rats were divided into three groups. Ten were fed standard rat chow for 5 weeks, 10, a fructose-enriched diet for 5 weeks, and 10, a fructose-enriched diet for 5 weeks, with rosiglitazone 10 mg/kg/d added during the last 2 weeks. Blood pressure (BP), oral glucose tolerance test (OGTT), plasma insulin, triglycerides, and adiponectin were recorded, as well as mRNA levels of the adiponectin gene in visceral adipose tissue. RESULTS: Fructose-fed rats developed MS as manifested by the increase in systolic BP (from 139 +/- 3 to 158 +/- 4 mm Hg, P < .05), insulin (from 26 +/- 1.6 to 40 +/- 2.5 muU/mL, P < .05), triglycerides (from 91 +/- 9 to 304 +/- 24 mg/dL, P < .05), and impaired OGTT (area under the curve from 13,894 +/- 246 to 17,725 +/- 700 mg/dL/min). Treatment with rosiglitazone reversed these effects and reduced BP to 133 +/- 7 mm Hg, insulin levels to 30 +/- 2.8 muU/mL, triglycerides to 116 +/- 9 mg/dL, and the OGTT to 15,415 +/- 372 mg/dL/min (P < .05 for all variables). In addition, rosiglitazone increased plasma levels of adiponectin fourfold from 4.3 +/- 0.1 to 18.4 +/- 0.6 mug/mL (P < .05). This increase was coupled with 3.8-fold increase in adiponectin mRNA in visceral adipose tissue. CONCLUSIONS: This study shows for the first time that in an animal model of MS, the insulin sensitizer, rosiglitazone, improves the metabolic profile and increases plasma levels of adiponectin and its gene expression. It is possible therefore that rosiglitazone exerts its beneficial effects by increasing the levels of adiponectin.

[Ambulatory blood pressure monitoring in diabetic hypertensive patients].

This study aimed to evaluate the frequency of attenuated decline in nocturnal blood pressure (BP) in diabetic hypertensive patients, and characterize those who don't decrease BP during nighttime. A total of 61 hypertensive patients (26 males and 35 females, mean age 65.8+/-10) were included in the study. Patients were defined as hypertensive if their daytime pressure exceeded 140/90 (the definition relevant at the time of our study) or if they were on antihypertensive treatment. All patients underwent 24 hour Ambulatory BP Monitoring (ABPM) using Suntech Accutracker Dx. Subjects with nocturnal fall in SBP, DBP or MAP of less than 10% of daytime values were classified as non-dippers. Echocardiography and renal function were also evaluated. Two thirds of the subjects were non-dippers. The percentage of dippers among women was higher than that observed in men: SBP 34% versus 19% and DBP 48% versus 38% (the difference is statistically significant with p< 0.01). Non-significant correlation was observed between absence of nocturnal decline, age and gender. The 24 hour ABPM measurements should be recommended in all diabetic hypertensive patients in whom aggressive treatment covering nighttime should be offered.

Peripartum hypertension from pheochromocytoma: a rare and challenging entity.

BACKGROUND: Pheochromocytoma, a rare and usually curable cause of hypertension, is characterized by symptoms and signs related to increased catecholamine secretion. Pregnancy can elicit clinical manifestations of otherwise unrecognized pheochromocytoma. METHODS AND RESULTS: Four women, ranging in age from 27 to 37 years, were referred to the hypertension clinic with the following presentations: 1) a 35-year-old woman, diagnosed with gestational hypertension and headaches during the third trimester of her pregnancy and 5 months after delivery, was hospitalized with pulmonary edema. Echocardiography revealed severe dilated left ventricular (LV) dysfunction. Cardiac function was normalized after surgical resection of a pheochromocytoma from her left adrenal; 2) a 37-year-old woman suffered from preeclampsia, persistent hypertension and orthostatic hypotension after a cesarean section. A diagnostic work-up revealed a catecholamine-secreting paraganglioma in the retroperitoneum. The patient underwent a laparosopic resection of the tumor; 3) a 27-year-old woman suffered from hypertension and episodes of palpitations, sweating, and dyspnea in the first trimester of her pregnancy. An ultrasound revealed a 5-cm mass in the left adrenal. She underwent a left adrenalectomy at the 17th week of pregnancy, which confirmed the diagnosis of pheochromocytoma; 4) a 34-year-old woman, at the 26th week of pregnancy, presented with an acute loss of vision and blood pressure of 230/140 mm Hg. Fundoscopy showed papilledema with soft exudates in both eyes. Chemical studies were positive and imaging revealed a left adrenal pheochromocytoma. Despite aggressive medical treatment, fetal distress mandated a laparotomy at the end of the 28th week of pregnancy. A healthy newborn was delivered and resection of the adrenal tumor confirmed the diagnosis of pheochromocytoma. CONCLUSIONS: Although rare, pheochromocytoma can cause severe peripartum hypertension. Screening for pheochromocytoma, ideally with plasma-free metanephrines, should be considered in cases of peripartum hypertension.

Does dietary recall adequately assess sodium, potassium, and calcium intake in hypertensive patients?

OBJECTIVE: A diet low in sodium, high in potassium, and high in calcium is recommended to lower blood pressure. However, compliance with this diet is poor, probably because of dietary intake underestimation. Therefore, we compared electrolyte intake as estimated from dietary recall with a 24-h urinary excretion. METHODS: Thirty-six patients (26 men and 10 women) with a mean age of 46 +/- 8 y participated in the study. All participants had essential hypertension and were on no drug therapy (n = 20) or non-diuretic monotherapy (n = 16). Patients were instructed to consume a low-sodium (50 mmol/d), high-potassium (supplementation with 30 to 60 mmol/d), and high-calcium (1000 mg/d) diet. Compliance with the diet was assessed at baseline and then 1, 2, and 3 mo after starting the diet. Sodium, potassium, and calcium intakes were carefully estimated from patients' dietary recall and 24-h urinary collection. RESULTS: Estimated sodium intake significantly correlated with 24-h urinary excretion (R = 0.43 P < 0.001). However, estimated sodium intake was lower than urinary sodium excretion by 34% at baseline and by 47% after 3 mo of dieting (P < 0.05). Estimated potassium intake correlated with 24-h urinary excretion. Estimated calcium intake significantly increased from 933 +/- 83 mg/d to 1029 +/- 171 mg/d (P < 0.05). Calcium intake derived from patients' recall far exceeded and only slightly correlated with 24-h urinary excretion (R = 0.23, P < 0.01). CONCLUSIONS: Patients tend to underestimate their sodium intake by 30% to 50%; therefore, urinary sodium excretion is more accurate to assess sodium intake. Thus, 24-h urinary sodium excretion should be used in clinical practice and in clinical trials, especially when dietary non-compliance is suspected.

Trandolapril and endothelin antagonist LU-135252 in the treatment of the fructose-induced hypertensive, hyperinsulinemic, hypertriglyceridemic rat.

BACKGROUND: In view of the demonstrated interaction between endothelin and the renin-angiotensin system, the antihypertensive effect of combined therapy with an endothelin antagonist LU-135252 and the angiotensin converting enzyme inhibitor trandolapril, was studied in fructose-induced hypertensive, hyperinsulinemic, hypertriglyceridemic male Sprague-Dawley rats. METHODS: Forty animals were fed a fructose-enriched diet (Tekled, Harlan) for 5 weeks, as follows: group A, fructose only; group B, trandolapril 0.1 mg/kg/day added during the last 2 weeks; group C, LU-135252 100 mg/kg/day added during the last 2 weeks; group D, both trandolapril and LU-135252 added the last 2 weeks. Systolic blood pressure (BP) was measured weekly in conscious rats by the indirect tail-cuff method. Blood samples from a retro-orbital sinus puncture were taken at the beginning of the experiment and after 3 and 5 weeks and examined for insulin and triglyceride concentrations. RESULTS: Systolic BP decreased in group B (trandolapril) from 148.8 +/- 9.8 at 3 weeks to 138.3 +/- 8.7 mm Hg after 5 weeks; in group C (endothelin antagonist) from 155.1 +/- 5.5 to 142.5 +/- 10.6 mm Hg; and in group D (combination) from 154.6 +/- 10.9 to 121.2 +/- 8.9 mm Hg. Triglyceride levels decreased only in the combined trandolapril/endothelin antagonist group from 167.6 +/- 55.3 in the third week to 134.9 +/- 53.7 mg/dL after 5 weeks. Insulin levels decreased only on combination therapy from 7.4 +/- 3.6 to 5.3 +/- 3.8 ng/mL during the same period. The BP decrease was additive compared with the respective individual substances. CONCLUSIONS: The trandolapril/endothelin antagonist combination appears to offer a rational antihypertensive combination that is superior to that of either drug alone. This finding applies to the specific rat model studied in which BP, insulin, and triglycerides were increased by fructose diet.

Oxidative stress in hypertensive,diabetic, and diabetic hypertensive rats.

BACKGROUND: Reactive oxygen species play a key role in the formation of endothelial dysfunction accompanying diabetes mellitus, hypertension, and other cardiovascular diseases. METHOD: This study compares oxidative stress (OS) in Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), non-insulin-dependent Cohen Diabetic rats (CDR), and Cohen Rosenthal diabetic hypertensive rats (CRDH), a unique animal model of both diabetes and hypertension. The OS was evaluated with a newly developed thermochemiluminiscence (TCL) analyzer (Lumitest Ltd., Nesher, Israel) that measures the oxidizability (ie, susceptibility to oxidation) of a test sample. RESULTS: The TCL oxidizability test results of sera from the different rats groups showed a time-dependent increase in TCL of up to 145% +/- 7% for WKY, 160% +/- 8% for SHR, 179% +/- 12% for CDR, and 226% +/- 15% for CRDH. These results were significant: P <.001 for SHR and CDR and P <.0001 for CRDH in comparison to WKY. Lipid peroxide levels also increased in each strain of rats: to 80 +/- 7.8 nmol/mL in WKY, 104 +/- 10.1 nmol/mL in SHR, 110 +/- 9.4 nmol/mL in CDR, and 167 +/- 11.7 nmol/mL in CRDH. These results were also significant: P <.001 for SHR, CDR and CRDH in comparison to WKY. CONCLUSION: The combination of hypertension and diabetes is accompanied by higher oxidative stress than that seen with either disorder alone.

Allylmercaptocaptopril: a new antihypertensive drug.

Allylmercaptocaptopril (CPSSA) was synthesized by reacting captopril with pure allicin. Fructose-induced hypertensive groups of rats were fed a fructose-rich diet for 3 weeks, and then received the diet plus either CPSSA (40 to 56 mg or 138 to 194 micromol/L/kg/d) or captopril (80 mg or 369 micromol/L/kg/d) for 2 more weeks. CPSSA (both doses) significantly lowered blood pressure (BP) from 153.4 to 120.8 mm Hg (P <.005). Captopril gave similar results, lowering BP from 150.7 to 123 mm Hg (P <.005). CPSSA also decreased the high levels of triglycerides to normal. The new stable compound allylmercaptocaptopril combines the beneficial properties of captopril and allicin and is a potential candidate for antihypertensive drug therapy.

The effects of allicin on weight in fructose-induced hyperinsulinemic, hyperlipidemic, hypertensive rats.

BACKGROUND: Commercially available garlic preparations in the form of garlic oil, garlic powder and pills are widely used for certain therapeutic purposes, including lowering blood pressure and improving lipid profile. Despite the impressive effects of garlic most studies are limited by lack of controlled methods and suitable double-blinding, and by the use of preparations with unknown amounts and chemical identification of the active ingredient. Allicin, a synthetic preparation of an active constituent of garlic, was found to lower blood pressure, insulin, and triglycerides levels in fructose-fed rats. Thus, it was considered important to assess its effect on the weight of the animals. METHODS: Male Sprague-Dawley rats weighing 240 to 250 g were fed a fructose-enriched diet consisting of 21% protein, 5% fat, 60% carbohydrate, 0.49% sodium and 0.49% potassium for 5 weeks, which produced hyperinsulinemia, hypertension, and hypertriglyceridemia. Group I (controls) rats were fed a diet enriched by fructose only; group II was given allicin the last 2 weeks, and group III was given allicin the first 3 weeks. The three groups consumed the same amount of food. Weight was measured at the beginning of the experiment and after 3 and 5 weeks on the diet. RESULTS: Weight in the control group rose from 249.4 +/- 10.04 g to 274.5 +/- 15.5 g after 3 weeks and to 306.9 +/- 22.2 g after 5 weeks. Weight in group II rose from baseline 259.1 +/- 12.1 g to 306.9 +/- 22.2 g after 3 weeks on fructose alone, and declined slightly to 282.4 +/- 17.4 g after 2 weeks of allicin (P <.02). In group III, in which the protocol was reversed, the baseline weight of 260.4 +/- 13.25 g rose only to 269.8 +/-15.3 g (P <.431) after 3 weeks on fructose and allicin. CONCLUSIONS: The control group that was fed a diet enriched by fructose alone continued to gain weight, whereas the groups fed allicin did not. The difficulty of preventing weight gain after reaching the nadir of weight loss underscores the practical value of allicin for weight control.

The correlation between isolated interventricular septal hypertrophy and 24-h ambulatory blood pressure monitoring in apparently healthy air crew.

BACKGROUND: Interventricular septal (IVS) hypertrophy is considered to affect prognosis in hypertensive patients. However, the natural history of isolated septal hypertrophy, identified by echocardiography in otherwise healthy subjects is not well defined. METHODS: The study population included 51 apparently healthy pilots with septal hypertrophy (septal thickness > 11 mm) defined by routine echocardiography, with a calculated normal left ventricular (LV) mass. All pilots underwent casual blood pressure (BP) measurements and a 24-h ambulatory BP monitoring (ABPM). Hypertension (HTN) was defined as a casual measurement of > 140/90 mmHg. RESULTS: The mean age of the pilots was 38 +/- 11 years and the body mass index (BMI) 26.3 kg/m(2). The 17 pilots found to be hypertensive had a higher septal thickness than the 34 counterparts with normal BP measurements (13.8 +/- 2.0 mm versus 12.6 +/- 1.7 mm, P < 0.04, respectively). The mean ambulatory daytime systolic and diastolic BP were higher in comparison to non-hypertensive pilots (142 +/- 6.2 versus 128 +/- 5.0 mmHg, P < 0.0001 for systolic BP and 91 +/- 5.3 versus 78 +/- 4.1 mmHg, P = 0.001 for diastolic BP), respectively. The adjusted relative risk (RR) of a subject with an IVS thickness P > 12 mm to be hypertensive by ABPM was 3.12 (95% confidence interval 1.04-9.37, P < 0.02). CONCLUSIONS: Isolated IVS hypertrophy, even in the presence of normal LV mass is associated with HTN. Screening healthy subjects at risk for hypertension by echocardiography enables one to identify those who should be closely monitored, using among others, ABPM.

Neutral endopeptidase inhibitor versus angiotensin converting enzyme inhibitor in a rat model of the metabolic syndrome.

The antihypertensive treatment in patients with metabolic syndrome is unclear. We therefore used a rat model of the metabolic syndrome and compared the effects of enalapril, an angiotensin-converting-enzyme inhibitor, with candoxatril, a neutral endopeptidase inhibitor that inhibits degradation of atrial natriuretic peptide and, in addition to lowering blood pressure, exerts metabolically beneficial activity. Ten male Sprague Dawley rats were fed regular rat chow for 5 weeks. Fifty male Sprague Dawley rats were fed a high-fructose diet for 3 weeks, followed by addition of enalapril, 10 mg/Kg/d, or candoxatril, 25, 50, or 100 mg/Kg/d, for 2 weeks. Systolic blood pressure, plasma triglyceride level, and insulin level were measured at baseline and after 3 weeks and 5 weeks. Three weeks of a high-fructose diet led to a significant increase in all metabolic parameters. Candoxatril and enalapril lowered systolic blood pressure significantly (candoxatril -10 ± 1 to -22 ± 1 mm Hg and enalapril -27 ± 2 mm Hg). High-dose candoxatril and enalapril significantly decreased plasma triglyceride levels (by 17.8% and 32.8%, respectively), but only high-dose candoxatril decreased plasma insulin levels significantly (by 25.3%). High-dose candoxatril is a metabolically favorable option for lowering blood pressure in a rat model of metabolic syndrome.

Blunted blood pressure response and elevated plasma adiponectin levels in female Sprague Dawley rats.

BACKGROUND: Premenopausal women have lower blood pressure (BP) levels than men of similar age. Adiponectin has been shown to play a role in the pathogenesis of hypertension. The aim of the present study was to compare the effect of various stress stimuli on BP and plasma adiponectin levels in male and female Sprague Dawley (SD) rats. METHODS: In three experimental models of hypertension, fructose-enriched diet, high salt diet, or L-NAME, were administered for up to 4 weeks. BP, metabolic parameters, and plasma adiponectin were measured at baseline and during the studies. The fructose diet protocol was repeated in female rats for 2 weeks with the addition of testosterone injections or vehicle. RESULTS: Females, in contrast to males, did not develop fructose-induced hypertension. Total plasma triglycerides (TGs) were half in females at baseline (P < 0.001) and a third at 4 weeks (P < 0.05). Plasma insulin levels were 23% lower in females than in males at baseline (P < 0.05) and 42% lower after 4 weeks of fructose-enriched diet (P = 0.001). Plasma adiponectin levels were 65% higher in females than in males at baseline (P = 0.001) and 45% higher after 4 weeks of fructose-enriched diet (P < 0.05). Furthermore, female rats showed blunted BP response and elevated plasma adiponectin in the salt-induced and L-NAME-induced hypertension models. Testosterone injection to female rats reduced plasma adiponectin and reversed the blunted BP response. CONCLUSIONS: Elevated plasma adiponectin levels, perhaps due to lack of suppression by testosterone, are associated with a blunting of BP response in female compared to male SD rats.

Orthostatic hypotension is associated with nocturnal change in systolic blood pressure.

BACKGROUND: The circadian pattern of blood pressure (BP) has yet to be defined among individuals with orthostatic hypotension (OH). The objective of this study was to evaluate whether OH is associated with nocturnal change in systolic BP. METHODS: In a prospective study, we evaluated patients who were referred for 24-h ambulatory blood pressure monitoring (ABPM). All subjects underwent orthostatic BP testing before recording their respective 24-h ABPM. RESULTS: The study includes 185 subjects, 114 males, mean age 58 ± 18 years (range 19-89). Participants were classified, based on pattern of systolic BP changes at night, as dippers (greater than 10% decrease; n = 74), nondippers (0-10% decrease; n = 77), and reverse-dippers (increase; n = 34). Nineteen patients (10.3%) had OH. Almost all participants with OH (95%) had an abnormal diurnal BP pattern, and most of them (58%) were reverse-dippers, whereas only 56% of the participants without OH had an abnormal diurnal BP variation, and only 14% were reverse-dippers (P < 0.001). Systolic BP decreased with upright posture by 12 and 2 mm Hg in the reverse-dippers and the nondippers, respectively, and increased by 2 mm Hg in the dippers (P < 0.001). Postural changes in systolic BP were inversely related to the changes between day and night BP readings(r = -0.43; P < 0.01). In a multivariate linear regression analysis, orthostatic BP change, use of ≥2 antihypertensive drugs and female sex were related to nocturnal BP changes. CONCLUSIONS: The decrease in BP during upright posture may be a marker of nondipping or reverse-dipping pattern of diurnal BP.