Red grape berry-cultured cells reduce blood pressure in rats with metabolic-like syndrome.

PURPOSE: Cumulative evidence suggests that moderate red wine consumption protects the cardiovascular system. The effect of cultured cells derived from red grape berry (RGC) on blood pressure (BP) has not been investigated. We therefore studied the antihypertensive effects of oral consumption of RGC in experimental rat model of metabolic-like syndrome and assessed its effect on human umbilical vein endothelial cells (HUVECs). METHODS: Forty male Sprague-Dawley rats were fed for 5 weeks with either a high fructose diet (HFD) (n = 10) or HFD supplemented, during the last 2 weeks, with different doses (200, 400 and 800 mg/kg/day) of RGC suspended in their food (n = 30). BP, plasma triglycerides, insulin and adiponectin levels were measured at the beginning and after 3 and 5 weeks of diet. RGC effect on vasodilatation was evaluated by its ability to affect endothelin-1 (ET-1) production and endothelial nitric oxide synthase (eNOS) expression in HUVECs. RESULTS: BP, plasma triglycerides, insulin and adiponectin increased significantly in rats fed with a HFD. The increase in BP, plasma triglycerides and insulin was attenuated by RGC supplementation. Incubation of HUVECs with RGC demonstrated a concentration-dependent inhibition of ET-1 secretion and increase in the level of eNOS, signaling a positive effect of RGC on vasodilatation. CONCLUSION: In rats with metabolic-like syndrome, RGC decreased BP and improved metabolic parameters. These beneficial effects may be mediated by the cell constituents, highly rich with polyphenols and resveratrol, reside in their natural state.

The effect of chronic hyperinsulinemia on plasma adiponectin levels in Sprague-Dawley rats.

Adiponectin is an important vascular protective substance whose levels are reduced in states of insulin resistance. The relationships between plasma insulin levels and adiponectin are not fully understood, and it is not known whether it is the elevated circulating levels of insulin or insulin resistance that directly affects adiponectin levels. The present study evaluates the direct effect of chronic hyperinsulinemia on plasma adiponectin levels. Male Sprague-Dawley rats were treated with insulin (n=15) administered by a sustained-release implant or were given a sham implantation (n=10) as a control group. Body weight, systolic blood pressure, plasma glucose, triglycerides, insulin, and adiponectin were measured at baseline and after 20 and 40 d of treatment. Insulin-treated rats and controls showed a similar increase in body weight. The insulin-treated group had a significant increase in plasma insulin levels and a decrease in plasma glucose levels compared with the sham group, with no change in blood pressure or triglyceride levels. Adiponectin levels remained unchanged despite the significant increase in insulin levels. High circulating insulin levels do not affect plasma adiponectin levels. These results support the concept that the primary defect that results in insulin resistance and hyperinsulinemia is responsible for the altered plasma adiponectin levels in the metabolic syndrome and type 2 diabetes.

Metabolic stress with a high carbohydrate diet increases adiponectin levels.

BACKGROUND: Adiponectin is an adipose tissue-specific protein, which possesses anti-atherogenic and antidiabetic properties, yet its plasma levels are decreased in subjects with metabolic syndrome. Although high fat diet has been linked to hypoadiponectinemia, the effect of high-carbohydrate diet on adiponectin levels is not known. Therefore, we studied the effect of high-carbohydrate diet on adiponectin levels in the rat models of hypertension and insulin resistance. METHODS: Rats were randomly assigned to the high carbohydrate diet [Sprague-Dawley rats with fructose enriched diet (SDR-F) and spontaneously hypertensive rats with sucrose enriched diet (SHR-S model)] or chow diet (Control group). Rats were followed for 6 weeks (SDR-F model) and 8 weeks (SHR-S model). Body weight, systolic blood pressure, plasma levels of glucose, insulin, triglycerides and adiponectin, were recorded. RESULTS: Both models were associated with features of the metabolic syndrome, namely, high insulin levels, increased blood pressure and triglyceride levels. Plasma adiponectin levels did not change in the control groups. In contrast, adiponectin levels increased by 39 and 30% compared to baseline following four and six weeks of fructose enriched diet in SDR (from 3.3+/-0.2 to 4.5+/-0.4 and 4.3+/-0.2 microg/ml, respectively, p<0.05). Likewise, five and eight weeks of sucrose enriched diet in SHR, induced a 54 and 81% increase in adiponectin levels compared to baseline (from 4.2+/-0.3 to 6.3+/-0.3 and 7.3+/-0.5 microg/ml, respectively, p<0.01). CONCLUSION: Metabolic stress with a high-carbohydrate diet increases plasma levels of adiponectin. Further studies will elucidate whether this is a transitory compensatory mechanism or a sign of target organ resistance to adiponectin.

Circulating adiponectin concentrations in patients with congestive heart failure.

OBJECTIVES: To determine concentrations of adiponectin and its predictive value on outcome in a cohort of patients with congestive heart failure (CHF). METHODS: Serum and clinical data were obtained for outpatients with clinically controlled CHF (n = 175). Serum concentrations of adiponectin, C reactive protein, N-terminal pro-brain natriuretic peptide (NT-proBNP), interleukin (IL) -1beta, IL-6, IL-8, IL-10, IL-12, tumour necrosis factor alpha and CD-40 ligand were determined. The association of adiponectin with the clinical severity of CHF was sought as well as the predictive value of this adipokine on mortality, CHF hospitalisations or the occurrence of each of these end points. RESULTS: Concentrations of adiponectin were significantly increased in patients with CHF. Patients with higher New York Heart Association class had significantly higher serum concentrations of adiponectin. Adiponectin serum concentrations were lower in patients with diabetes and CHF as well as in patients with ischaemic cardiomyopathy. Serum adiponectin concentration was positively associated with age and NT-proBNP but was negatively correlated with C reactive protein concentrations. Serum adiponectin above the 75th centile was found to be an independent predictor of total mortality, CHF hospitalisations or a composite of these end points over a two-year prospective follow up. CONCLUSION: Adiponectin is increased in CHF patients and predicts mortality and morbidity.

[Periodontal-endodontal interactions].

The periodontal ligament and the root canals system have a common developmental, anatomical and functional link. Those include the apical foramina, accessory canals and dental tubules whereas the pathological pathways perforation and vertical fractures. Similar microflora- bacteria, virus and yeast also have documented at the both nisus. This article describes the influence of the periodontium on the pulp and vise versa. The pulp is highly survivable and posses high ability to sustain the disease and treatment and periodontal disease and periodontal treatment exhibit small effect on the pulp. However, pulp necrosis is a risk factor to damage the periodontal ligament of the teeth.

Enterobacter cloacae, an obligatory endophyte of pollen grains of Mediterranean pines.

Enterobacter cloacae was found to be associated with the pollen of several Mediterranean pines. The bacterium was detected only in mature pollen of Pinus halepensis, P. brutia, and P. pinea. E. cloacae is considered to be an obligatory endophyte based on its occurrence in disinfected male cones and the successful inoculation of seedlings of the above 3 species with E. cloacae AS1 isolated from pollen of P. halepensis used as a model strain. Strain AS1 was able to produce indolyl-3-acetic acid (IAA) from L-tryptophan in culture, and this was probably the source of the increased IAA content in the germination medium of pollen. In addition, strain AS1 promoted adventitious root formation in mung bean (Vigna radiata) cuttings. However, it was not possible to obtain bacterium-free pollen to elucidate its role in pollen germination.

Chronic exogenous hyperinsulinaemia-induced hypertension in pregnant rats: effect of chronic treatment with l-arginine.

Recent studies have shown that maternal hyperinsulinaemia is a risk factor for the development of hypertension in pregnancy. Experimentally, pregnant rats with chronic exogenously induced hyperinsulinaemia (P-INS rats) have increased blood pressure at the end of gestation. This is associated with a blunted elevation of the excretion of the urinary metabolites of nitrate (UNO(x)). In the present study, we aimed to evaluate the mechanism(s) of the increase in blood pressure in this model. Four groups were studied: normal pregnant rats (P rats), P-INS rats, P-INS rats treated with L-arginine (2 g/l in the drinking water) (L-ARG rats) and hyperinsulinaemic virgin rats (V-INS rats). Systolic blood pressure (SBP), UNO(x) excretion (on ingestion of a controlled low-nitrate diet), urine noradrenaline (norepinephrine) and plasma endothelin levels were evaluated. Rats were killed on day 22 of pregnancy. Five P-INS rats were not killed at this time, in order to measure SBP 30 and 60 days after delivery. Fetal number and fetal body weight were evaluated. At the end of pregnancy, a 10+/-3% increase in SBP was found in P-INS rats, contrasting with a fall of -15+/-4% in P rats (P<0.01). In the L-ARG group at the end of pregnancy, SBP values had fallen by -14+/-2%, to values comparable with those of P rats. The increase in UNO(x) excretion was 175+/-38% in P rats, 106+/-12% in L-ARG rats and 41+/-8% in P-INS rats (P<0.01 compared with P and L-ARG groups). No differences were found in the urinary excretion of noradrenaline or in the plasma levels of endothelin-1 between the pregnant groups. Fetal number was similar in all groups, but fetal body weight was lower for P-INS rats compared with P and L-ARG rats. Thus the blood pressure response to L-arginine strongly suggests that a decrease in NO availability may be the main pathogenic mechanism involved in the development of hypertension in this model.

The effects of allicin and enalapril in fructose-induced hyperinsulinemic hyperlipidemic hypertensive rats.

The effects of a synthetic preparation of an active constituent of garlic, allicin, were studied on blood pressure (BP), triglycerides, and insulin levels in Sprague-Dawley rats in which high fructose feeding elicited hyperinsulinemia, hypertension, and hypertriglyceridemia. Results were compared with those of the antihypertensive drug enalapril. Three groups of male Sprague-Dawley rats were fed a fructose-enriched diet for 5 weeks. During the last 2 weeks 10 animals received only fructose, 10 received allicin, and 10 received enalapril. Blood pressure, insulin level, and triglyceride levels were measured at the beginning of the experiment and after 3 and 5 weeks on the fructose diet, fructose/allicin diet, or fructose/enalapril diet. Allicin lowered BP from the maximal level (after 3 weeks of fructose) of 153.4 +/- 8 mm Hg to 139.7 +/- 12 mm Hg after 2 weeks on allicin; insulin from 11.7 +/- 3.7 ng/mL on fructose diet to 6.92 +/- 3.3 ng/mL on allicin; and triglycerides from 132.8 +/- 18 mg/dL on fructose to 59.6 +/- 27 mg/dL on allicin. The similar effect of allicin and enalapril on BP, insulin, and triglycerides reinforces the trend toward combining the nonpharmacologic approach with drug therapy.

Device-guided breathing exercises reduce blood pressure: ambulatory and home measurements.

Slow breathing practiced routinely using an interactive device has demonstrated a sustained reduction in high blood pressure (BP). We reevaluated the BP response of hypertensives (n = 13) to this daily treatment for 8 weeks using 24-h ambulatory, home, and office BP measurements. A clinically significant BP reduction of similar magnitude was observed in all BP monitoring modalities during the daytime. Greater BP reductions were found for older patients and higher baseline BP. The results provide additional support for the efficacy of the device as an adjunctive lifestyle modification for treating hypertension.

Subpressor dose of L-NAME unmasks hypertensive effect of chronic hyperinsulinemia.

We previously found that chronic exogenous hyperinsulinemia without sugar supplementation does not elevate blood pressure. This may be partially explained by the ability of insulin to release nitric oxide and cause vasodilatation. To test this hypothesis, we studied 4 groups of rats: 9 rats (body weight, 213+/-14 g) treated with a gradual increase of a sustained-release subcutaneous insulin pellet; 9 rats (body weight, 213+/-9 g) treated with N:(G)-nitro-L-arginine methyl ester (L-NAME) in drinking water 50 mg/L; 19 rats (body weight, 217+/-11 g) treated with the combination of L-NAME and insulin; and 9 control rats (body weight, 218+/-11 g). Blood pressure was followed weekly for 6 weeks, and then rats were studied in metabolic cages. Weight gain was not different during the 6 weeks. Renal function did not differ between the 4 groups, but 24-hour urinary nitrite/nitrate excretion was lower (P<0.02) in L-NAME-treated and higher in insulin-treated rats. Plasma insulin doubled (P<0.002) in the insulin-treated rats, but there was no hypoglycemia and, by week 6, fructosamine levels were 2.1+/-0.2, 2.1+/-0.2, 2.3+/-0.1, and 2.3+/-0.2 mmol/L in control rats and rats treated with L-NAME, insulin, and L-NAME plus insulin, respectively. Systolic blood pressure, which did not differ at baseline, at week 3 was 122+/-17, 118+/-17, and 118+/-24 mm Hg in the control, L-NAME, and insulin groups and 136+/-14 mm Hg (P<0.03) in the combination group. At week 6, systolic blood pressure was 128+/-14, 127+/-15, and 118+/-13 mm Hg in the control, L-NAME, and insulin groups, respectively, and 150+/-14 mm Hg (P<0.0005) in the combination group. In a subsequent experiment, L-arginine 2 g/L abrogated the effects of L-NAME and insulin combination. In conclusion, chronic exogenous hyperinsulinemia does not affect blood pressure but may cause hypertension when endothelial function is compromised.

Conversion of recent onset paroxysmal atrial fibrillation to normal sinus rhythm: the effect of no treatment and high-dose amiodarone. A randomized, placebo-controlled study.

BACKGROUND: Spontaneous conversion of recent onset paroxysmal atrial fibrillation to normal sinus rhythm occurs commonly and is not affected by low-dose amiodarone treatment. METHODS: In a randomized, placebo-controlled trial of 100 patients with paroxysmal atrial fibrillation of recent onset (<48 h) we compared the effects of treatment with continuous intravenous amiodarone 125 mg per hour (total 3 g) and intravenous placebo. Patients in the placebo group who did not convert to normal sinus rhythm within 24 h were started on amiodarone therapy. RESULTS: Conversion to normal sinus rhythm occurred within 24 h in 32 of 50 patients (64%) in the placebo group, most of whom converted within 8 h. Lower conversion rates were observed in patients with hypertension, ischaemic heart disease or congestive heart failure and in patients with echocardiographic findings of left atrial diameter above 45 mm, ejection fraction below 45% or significant mitral regurgitation. However, in most patients these clinical or echocardiographic risk factors of decreases in conversion rate were not present. In such patients the spontaneous conversion rate was approximately 90%. The conversion rate during 24 h of treatment in the amiodarone group was 92% (P=0.0017, compared to the placebo group). In this group, the conversion rate was largely unaffected by baseline characteristics. Of the 18 patients who did not convert with placebo, 15 (85%) converted after being crossed over to amiodarone. All patients not responding to high-dose amiodarone were in chronic atrial fibrillation within 1 month. In patients still in atrial fibrillation after 8 h of treatment, the pulse rate decreased significantly more in the amiodarone as compared to the placebo group (83+/-15 vs 114+/-20 beats. min(-1), P=0.0014). CONCLUSION: The spontaneous conversion of recent onset paroxysmal atrial fibrillation is high and approaches 90% in specific clinical and echocardiographically defined subgroups. Intravenous high-dose amiodarone safely facilitates conversion of paroxysmal atrial fibrillation. However, such treatment should be reserved for patients with unfavourable risk factor profiles, not converting during 8 h of observation or requiring rate control.

Effect of a mineral salt diet on 24-h blood pressure monitoring in elderly hypertensive patients.

The influence of a mineral salt on 24-h ambulatory blood pressure (BP) monitoring was studied in 20 elderly hypertensive subjects residing in an old peoples home. Ordinary table and cooking salt was substituted with a special Na-reduced, K-, Mg-, and l-lysine HCl-enriched mineral salt (Pansalt(R)) for 6 months. Antihypertensive therapy was uninterrupted. An ambulatory BP monitor (Suntech Accutracker) measured BP every 20 min during the day and every 30 min at night, before and 6 months after starting the diet. Nine patients (45%) decreased both systolic and diastolic BP significantly: systolic BP fell from 154.92 +/- 33.67 mm Hg to 143. 45 +/- 53.1 mm Hg (P < or = 0.01) during the daytime from 6 am to midnight; and from 139.80 +/- 32.84 mm Hg to 137.87 +/- 31.17 mm Hg (P < or = 0.01) from midnight to 6 am. Diastolic BP fell from 85.34 +/- 24.85 mm Hg to 70.29 +/- 18.31 mm Hg (P < or = 0.01) during the daytime from 6 am to midnight; and from 77.1 +/- 22.92 mm Hg to 67.76 +/- 15. 63 mm Hg (P < or = 0.01) at night. Blood pressure in the other 11 subjects showed no improvement. Heart rate also fell in the subjects, from 69.44 +/- 21.62 beats per minute (bpm) to 66.94 +/- 11.51 bpm (< or = 0.01) during the day, and from 61.28 +/- 12.82 bpm to 60.43 +/- 10.33 bpm (P < or = 0.01) during the night. It is concluded that decreased intake of Na and increased intake of both K and Mg can be useful in controlling high BP.

Renal effects of L-DOPA in heart failure.

We examined whether low-dose L-DOPA treatment induces natriuresis and diuresis in patients with congestive heart failure who have cardiac decompensation despite treatment with digoxin, a diuretic, and an angiotensin-converting enzyme inhibitor and who respond acutely to intravenously infused dopamine. In a randomized, double-blind, placebo-controlled crossover study, 11 patients with severe congestive heart failure received L-DOPA (0.10 g, p.o., t.i.d., for 1 day and then 0.25 g, p.o., t.i.d., for 2 days after a washout period of > or = 1 day), with assessments of plasma and urinary levels of catechols, urinary volume, and sodium content, and clinical and laboratory measures of improvement of congestive heart failure. L-DOPA elicited short-term, dose-related increases in urinary volume and sodium excretion. At the 0.10-g dose, L-DOPA increased plasma L-DOPA levels and urinary L-DOPA excretion by about fivefold, whereas at the 0.25-g dose, L-DOPA increased plasma and urinary L-DOPA by >50-fold. Twenty-four-hour urinary dopamine excretion increased by about fivefold after the low dose of L-DOPA and approximately 50-fold after the high dose. The results demonstrate that oral L-DOPA treatment can produce beneficial natriuretic and diuretic effects in selected patients with congestive heart failure. The bioavailability of oral L-DOPA appears to vary with the dose. These results support findings from previous studies about beneficial cardiac functional effects of L-DOPA in patients with refractory heart failure.

Elevated plasma atrial natriuretic peptide levels after occlusion of the thoracic aorta.

STUDY OBJECTIVE: The influence of occlusion of the thoracic aorta by an intraluminal balloon on plasma atrial natriuretic peptide (ANP) levels was evaluated in humans. METHODS: The changes in plasma ANP and plasma norepinephrine levels, and hemodynamic parameters were measured in 10 patients under general anesthesia undergoing regional chemotherapy treatment involving the 15-min inflation and subsequent deflation of an intraaortic balloon. RESULTS: The hemodynamic changes observed were similar to those seen during aortic clamping and declamping in patients undergoing vascular surgery. Plasma ANP levels (median+/-SD) measured 1 min after inflation (146+/-117 pg/mL) and 1 min after deflation (168+/-189 pg/mL) of the aortic balloon were significantly higher than baseline values (83+/-55 pg/mL), with a mean increase, respectively, of 92% and 97% (95% confidence intervals [CI], 50 to 147% and 53 to 152%). Plasma ANP levels were still elevated 30 min after deflation (121+/-94 pg/mL), a 56% increase (95% CI, 21 to 100%), although the hemodynamic parameters had already returned to their baseline levels. There was no evidence that the hemodynamic variables were associated with changes in plasma ANP levels (all p values > 0.30). In addition, there was no evidence of an association between plasma ANP and plasma norepinephrine levels at any of the four individual sampling points (p > 0.17). Thirty minutes after deflation, however, norepinephrine levels were higher than baseline values. CONCLUSIONS: The changes in plasma ANP levels after aortic occlusion and reinstitution of blood flow may be dependent on parameters other than atrial stretch and pressure.

Stress reaction to intense sound exposure under different arousal levels in guinea pigs.

The general impact of high intensity sound exposure on 25 guinea pigs was investigated at three different levels of arousal: 10 during general anaesthesia. 10 during partial arousal, and 5 during complete arousal. Parameters recorded before and during noise exposure were mean arterial blood pressure, pulse rate, and plasma norepinephrine levels. The anaesthetized group showed no increase in the three parameters during sound exposure. Under partial arousal, pulse rate and norepinephrine level increased significantly: pulse rate from 224.5 beats/min before exposure to 278.6 beats/min during exposure, and norepinephrine level from 558 pg/ml before sound exposure to 1276 pg/ml during exposure. At the time of the complete arousal state norepinephrine and pulse rates increased significantly during noise exposure, while blood pressure showed no additional increase as a result of sound exposure.

Enhanced erythrocyte Na+/H+ exchange predicts diabetic nephropathy in patients with IDDM.

Diabetic nephropathy develops in a subset of patients with an apparently hereditary predisposition. Microalbuminuria and elevated arterial pressure have been proposed as predictors of nephropathy but both appear when renal damage is impending. Enhanced sodium-hydrogen exchange in the cell membranes of diabetic patients is an early marker of diabetic nephropathy but its predictive value has not been assessed. In this study, sodium-hydrogen exchange was measured in erythrocytes as an initial velocity of amiloride-inhibited H+ efflux (pH 6.35-6.45) into a Na+ - containing medium (pH 7.95-8.05) in 156 non-microalbuminuric insulin-treated diabetic patients (98 women, 58 men, age 33+/-8 years, diabetes duration prior to enrollment 15+/-4 years) during 8 years of follow-up. Enhanced erythrocyte sodium-hydrogen exchange predicted diabetic nephropathy alone and in association with a familial tendency to hypertension/nephropathy with 86 and 96% sensitivity, and 80% specificity. Thus, sodium-hydrogen exchange appears to detect a subset of diabetic patients prone to develop renal damage, in whom a more intensive treatment modality might be considered.

The effect of caffeine on ambulatory blood pressure in hypertensive patients.

Because the potential impact of habitual caffeine intake on blood pressure is a controversial issue, a study was carried out to explore the relationship between caffeine and various humoral factors that could account for a coffee-induced rise in blood pressure. Twenty-three hypertensive patients who refrained from caffeine for 2 to 3 weeks were given 250 mg oral caffeine powder dissolved in water. Blood pressure was recorded every 15 min by blood pressure monitor. Caffeine blood level, renin and endothelin were measured before and 1, 2, 3, and 6 h after caffeine intake. Urinary electrolytes and catecholamines were measured under caffeine influence (period I), and for the next 6 h (period II). A significant increase in systolic (P = .017) and diastolic blood pressure (P = .023) occurred in 13 subjects who were 58 +/- 10.4 years old. Nonresponders were younger (44.5 +/- 15.8 years). A statistically significant decrease in heart rate was seen during the first hour after caffeine intake in both responders (P = .008) and nonresponders (P = .004). Marked diuresis and natriuresis were observed during period I in both groups. Renin and endothelin levels were unchanged. Although chronic studies point to development of tolerance to long-term caffeine ingestion, acute studies like the one described are essential to obtain data on the immediate effects that can be of practical importance, especially in the elderly.

Membrane ion transport in Bartter's syndrome: evidence for a new syndrome subtype.

Fifteen patients with Bartter's syndrome (hyponatremic hypochloremic hypokalemic metabolic alkalosis) were compared with 15 healthy volunteers. Red blood cell Na+/H+ and Cl-/HCO3- exchanges were enhanced in all patients with Bartter's syndrome. In calciuric normomagnesemic patients, sensitive to nonsteroidal anti-inflammatory drugs (classic Bartter's syndrome), red blood cell Na+,K+,2Cl- cotransport was markedly reduced, calcium-dependent K+ permeability was moderately increased, and up to 60% of sodium permeability was represented by cAMP-activated fraction (presumably human analog of beta-isoform of Na+/H+ exchange). In noncalciuric hypomagnesemic patients insensitive to indomethacin (Gitelman's syndrome), Na+,K+,2Cl- cotransport was enhanced, Na+ permeability was increased due to calmodulin-dependent fraction, and calcium-dependent K+ permeability was markedly enhanced. A new subtype of Bartter-like syndrome ("variant Bartter's syndrome") has been described in which calciuria, hypomagnesemia, and insensitivity to nonsteroidal anti-inflammatory drugs were associated with decreased Na+,K+,2Cl- cotransport, enhanced calmodulin-activated fraction of Na+ influx, and reduced calcium-dependent K+ permeability.