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.

Effects of salts and ionophores on proline transport in a moderately halopholic halotolerant bacterium.

The effect of salt on proline uptake in a moderately halophilic halotolerant bacterium was studied. Cells were grown either on low salt or high salt media. A correlation was found between the salt concentrations in the growth media and the optimal concentration for uptake. The uptake rate was stimulated 2--3-fold by NaCl, as compared to KCl. The Km, V and activation energies values for proline uptake, as well as the external pH effect, were similar in low-salt-grown cells and high-salt-grown cells. This suggests that the halotolerance of the transport system is not due to alterations of the system during growth at various conditions, but rather to its intrinsic ability to function under extreme environmental conditions. The uptake was inhibited by cyanide and carbonyl cyanide m-chlorophenylhydrazone, but not by arsenate, indicating that the electrochemical proton gradient (delta mu- H+), generated by respiration, is the main driving force for proline transport. In low-salt-grown cells, at pH 6.0, partial inhibition was exerted by nigericin or valinomycin, whereas at pH 8.0 the uptake was inhibited by valinomycin only. Similar, although less pronounced effects were found in high-salt-grown cells. The data suggest that at pH 6.0 proline transport is driven by delta mu- H+ (composed of electrical potential (delta psi) and pH gradient), whereas at pH 8.0 delta psi is the main driving force. Procedures of pretreatment with EDTA were developed to enable the penetration of the ionophores into the cells.

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.

[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.

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.

Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy.

PURPOSE: We have previously found thiamine (vitamin B1) deficiency in patients with congestive heart failure (CHF) who had received long-term furosemide therapy. In the present study, we assessed the effect of thiamine repletion on thiamine status, functional capacity, and left ventricular ejection fraction (LVEF) in patients with moderate to severe CHF who had received furosemide in doses of 80 mg/d or more for at least 3 months. PATIENTS AND METHODS: Thirty patients were randomized to 1 week of double-blind inpatient therapy with either i.v. thiamine 200 mg/d or placebo (n = 15 each). All previous drugs were continued. Following discharge, all 30 patients received oral thiamine 200 mg/d as outpatients for 6 weeks. Thiamine status was determined by the erythrocyte thiamine-pyrophosphate effect (TPPE). LVEF was determined by echocardiography. RESULTS: TPPE, diuresis, and LVEF were unchanged with i.v. placebo. After i.v. thiamine, TPPE decreased (11.7% +/- 6.5% to 5.4% +/- 3.2%; P < 0.01). LVEF increased (0.28 +/- 0.11 to 0.32 +/- 0.09; P < 0.05), as did diuresis (1,731 +/- 800 mL/d to 2,389 +/- 752 mL/d; P < 0.02), and sodium excretion (84 +/- 52 mEq/d to 116 +/- 83 mEq/d, P < 0.05). In the 27 patients completing the full 7-week intervention, LVEF rose by 22% (0.27 +/- 0.10 to 0.33 +/- 0.11, P < 0.01). CONCLUSIONS: Thiamine repletion can improve left ventricular function and biochemical evidence of thiamine deficiency in some patients with moderate-to-severe CHF who are receiving longterm furosemide therapy.

The role of atrial natriuretic peptide in natriuresis of fasting.

OBJECTIVE: To examine the relation between plasma atrial natriuretic peptide (ANP) and the natriuresis of fasting. DESIGN: ANP, aldosterone and renin were examined during natriuresis of fasting in 25 obese essential hypertensive patients and nine overweight normotensive subjects placed on a supervised 500-KCal diet composed of 50% carbohydrates, 30% fat and 20% protein, and unlimited salt. Twenty-four-hour urinary electrolytes were measured on days 0, 4, 7 and 10 of the diet. RESULTS: Urinary sodium concentration nearly doubled in the patients on day 4, and increased 1.4-fold in the normotensive controls. Plasma ANP rose nearly threefold in the hypertensives on day 4 and nearly doubled in the normotensives. Patients and controls showed similar patterns of natriuresis and ANP secretion during the diet. CONCLUSIONS: We conclude that there is a clear association between ANP levels and natriuresis of fasting.

Ventricular arrhythmias in rehabilitated and nonrehabilitated post-myocardial infarction patients with left ventricular dysfunction.

The incidence of ventricular arrhythmias in rehabilitated post-myocardial infarction (MI) patients with left ventricular dysfunction included in a long-term rehabilitation program was assessed and compared with that in similar patients who were not in such a program. Thirty-eight post-MI patients (2 to 19 years after the acute event) with ejection fraction < 40% were investigated by 48-hour Holter monitoring. They were divided into the following 3 groups: group I, 11 patients who underwent arm training for 60 months; group II, 11 patients who underwent calisthenics for 36 months; and group III, 16 patients who were not in any rehabilitation program; the age of the patients was 61 +/- 7, 61 +/- 6 and 61 +/- 9 years, respectively, (p = not significant). Ejection fraction at rest was 31 +/- 9 for group I, 29 +/- 7 for group II, and 29 +/- 7 for group III (p = not significant). There were no significant differences concerning the location of MI, and antiarrhythmic treatment received by patients from all groups. At the conclusion of 48-hour Holter monitoring, 2 blood samples were obtained for assessment of norepinephrine (at rest and after postural change). Quality of life was determined by a detailed questionnaire, including questions concerning social activity, life satisfaction and sexual function. After 36 and 60 months, an improvement in hemodynamic condition of patients in group I was noted. Quality of life was higher in the rehabilitated patients, with enhanced emotional stability, satisfaction with work and social life, and a high percentage of return to work (82 vs 40%).(ABSTRACT TRUNCATED AT 250 WORDS)

The perioperative fate of residual gradients after repair of discrete subaortic stenosis and time-related blood levels of catecholamines.

UNLABELLED: The fate of the residual peak systolic left ventricular-aortic gradient was studied perioperatively in 14 patients with membranous discrete subaortic stenosis. In nine (group A) the initial postrepair left ventricular-aortic gradient was greater than 35 mm Hg (mean 56.8 +/- 13.4), and in five (group B) there was no significant postoperative gradient (mean 15.3 +/- 3.2 mm Hg). The operation included membranectomy and myectomy. Peak left ventricular-aortic pressure gradient, endogenous levels of norepinephrine, peak rate of rise of left ventricular pressure, cardiac index, systemic vascular resistance, heart rate, and central venous pressure were recorded at the end of cardiopulmonary bypass and in 3-hour intervals for the next 9 hours. In group A during that period there was a 67% reduction in peak systolic left ventricular-aortic gradient (from 56.8 +/- 13.4 to 18 +/- 14 mm Hg, p less than 0.001). Concomitant reduction in the initial endogenous norepinephrine level was observed (from 982.1 +/- 181 to 422.6 +/- 109 pg/ml, p less than 0.001). A consistent linear relationship between norepinephrine levels and peak systolic left ventricular-aortic gradient was found (r = 0.78). Systolic left ventricular pressure decreased from 174.2 +/- 24.8 to 113.8 +/- 14.7 mm Hg (p less than 0.001). Marked reduction in peak rate of rise of left ventricular pressure (from 3455 +/- 636 to 2161 +/- 680 mm Hg/sec, p less than 0.001) was observed. Cardiac index increased and systemic vascular resistance decreased during the study period (from 2.11 +/- 0.2 to 3.07 +/- 0.26 L/min, p less than 0.001, and from 2172 +/- 331 to 1233 +/- 202 dynes/sec/cm-5, p less than 0.001, respectively). There were no significant changes in heart rate (p = not significant) and central venous pressure p = not significant). CONCLUSION: Some of the residual perioperative left ventricular-aortic gradients in patients with discrete subaortic stenosis undergoing repairs are dynamic and transient, and are probably related to increased postoperative sympathetic activity.

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.

The hypertensinogenic activity of 18-hydroxy-19-norcorticosterone in the adrenalectomized rat.

Hypertensinogenic properties of recently synthesized 18-OH-19-nor-B and the related 18-OH-B were examined in adrenalectomized, spontaneously hypertensive rats (SHR). Each steroid was given via Alzet miniosmotic pump (2002), with and without aldosterone. Neither 18-OH-19-nor-B (5 micrograms) nor 18-OH-B (5 micrograms) increased blood pressure in SHR when given alone, but when administered together with aldosterone (5 micrograms), which was ineffective by itself, resulted in a significant rise in blood pressure. There is a high probability that certain mineralocorticoids, which are inactive by themselves, are of importance in the etiology of hypertension under physiological conditions.

Hemodynamic and neurohumoral effects of fish oil in hypertensive patients.

Recent studies showed that supplementation of a large dose of fish oil is effective in lowering blood pressure. Whether supplementation of a low dose of fish oil is also effective in lowering blood pressure is controversial. The present study evaluates the hemodynamic and humoral effects of low-dose dietary fish oil supplementation in patients with mild hypertension. Eleven patients with mild hypertension were given 3 g/day of n-3 polyunsaturated fatty acids for 6 week. Twenty-four hour blood pressure monitoring and humoral parameters were recorded before and during fish oil treatment. In five patients, blood pressure response to angiotensin II (AII) infusion (1, 2, 3, 6, 9 ng/kg/min) was also recorded before and during treatment. Casual mean arterial pressure was unchanged (111 +/- 1 mm Hg v 109 +/- 3 mm Hg; P = NS). Average 24-h mean arterial pressure (MAP) also did not change during fish oil treatment (98 +/- 2 mm Hg v 99 +/- 3 mm Hg; P = NS). Fish oil supplementation did not attenuate the vascular reactivity to AII infusion. Maximal MAP following AII infusion (9 ng/kg/min) was 128 +/- 5 mm Hg before and 129 +/- 7 mm Hg during fish oil treatment (P = NS). Plasma levels of norepinephrine, renin activity, aldosterone, and atrial natriuretic peptide remained unchanged during treatment. Plasma levels of total cholesterol slightly increased from 200 +/- 10 mg/dL to 211 +/- 9 mg/dL (P < .05), but plasma levels of high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides were unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

Hemodynamic and humoral effects of the angiotensin II antagonist losartan in essential hypertension.

Losartan (DuP 753) is a novel orally active angiotensin II antagonist that lowers blood pressure. The present study evaluates the hemodynamic and humoral effects of losartan in essential hypertension. Fifteen patients (12 men, 3 women; mean age, 46 +/- 2 years; range, 33 to 64 years) with a diastolic blood pressure (DBP) between 95 and 115 mm Hg after 2 weeks of placebo participated in the study. Initially the patients were treated with losartan (50 mg) once daily for 1 month. Then, if the trough DBP was > or = 93 mm Hg, hydrochlorothiazide (HCTZ), 6.25 to 12.5 mg daily, and nifedipine, 30 to 60 mg daily, were added as needed. Ten patients completed 12 months of treatment. Trough blood pressure, heart rate, plasma creatinine, potassium, uric acid, cholesterol, renin activity (PRA), aldosterone, and norepinephrine were measured at baseline and after 1 and 12 months of treatment. Losartan lowered mean arterial pressure significantly from 119 +/- 2 mm Hg at baseline to 113 +/- 2 mm Hg (P < .05) after 1 month of treatment. Coadministration of HCTZ and nifedipine further decreased the mean arterial pressure to 103 +/- 2 mm Hg after 12 months of treatment. Plasma levels of creatinine, potassium, uric acid, cholesterol, and norepinephrine remained unchanged. PRA increased and plasma aldosterone decreased significantly (P < .05). The decrease in mean arterial pressure was related to baseline PRA (r = 0.53, P < .05). and to the change in PRA (r = 0.52, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of enalapril with and without hydrochlorothiazide on insulin sensitivity and other metabolic abnormalities of hypertensive patients with NIDDM.

The effect of 20 mg of enalapril with and without 12.5 mg of hydrochlorothiazide on glucose metabolism insulin sensitivity and lipids was evaluated in hypertensive non-insulin-dependent diabetes. Ten mild to moderate hypertensive patients with non-insulin-dependent diabetes mellitus were treated for 8 weeks with 20 mg enalapril once a day, and then divided into two groups of 5 patients each for a second 8 weeks of treatment with enalapril alone or in combination with hydrochlorothiazide, 12.5 mg once a day. Blood pressure, fasting plasma glucose, lipids and insulin, glycosylated hemoglobin, and insulin sensitivity were measured at baseline and after 8 and 16 weeks. Results were analyzed by the ANOVA test for repeated measures and all values are given as mean +/- SD. Diastolic blood pressure decreased significantly after the first and second period of enalapril and after the combination of enalapril and hydrochlorothiazide. Glycosylated hemoglobin dropped significantly after the first and second period of enalapril monotherapy. Plasma triglycerides and fasting plasma insulin decreased significantly after the 16 weeks of enalapril. Insulin-mediated glucose uptake increased significantly after 8 and 16 weeks of monotherapy with enalapril. No significant difference was observed in any of the metabolic characteristics, including insulin sensitivity, between the values after 8 weeks of enalapril alone and the final values of the enalapril-treated and the enalapril/hydrochlorothiazide-treated groups. It is concluded that enalapril improves some of the metabolic parameters, including insulin sensitivity, of hypertensive diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The hypertensinogenic activity of 18,19-dihydroxycorticosterone in adrenalectomized rats.

Adrenalectomized, spontaneously hypertensive rats (SHR) were used to test the hypertensinogenic property of recently synthesized 18,19-dihydroxycorticosterone (18,19-Di-OH-B). The steroid was given via Alzet miniosmotic pump, with and without aldosterone. Neither 18,19-Di-OH-B (5 micrograms) nor aldosterone (5 micrograms) increased blood pressure in SHR when given alone; when administered together they resulted in a significant rise in blood pressure. Results indicate a high probability that certain mineralocorticoids, which are inactive by themselves, might play a role in the etiology of hypertension when acting together under physiological conditions.

Urinary output of urodiolenone in essential hypertension.

Increased amounts of urodiolenone, an isomer of a phytoalexin, were found in the urine of 34% of patients with essential hypertension. Urodiolenone was also excreted in 70% of patients with neurocirculatory asthenia (hyperkinetic syndrome) and labile hypertension; very small quantities were found in normal subjects. When grapefruit juice, which is rich in urodiolenone, was offered to hypertensive subjects, urodiolenone excretion was much higher than the amount ingested, indicating that output was not due to precursors present in the diet.

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.

The role of atrial natriuretic peptide in the diuretic effect of Ca2+ entry blockers.

The effect of three calcium entry blockers--verapamil, nifedipine and felodipine--on diuresis, natriuresis, the renin-aldosterone axis, and atrial natriuretic peptide (ANP) levels was studied in 30 previously untreated patients with mild to moderate essential hypertension. All three blockers produced significant antihypertensive effects after 2 and after 24 h. Heart rate tended to decrease, but did not change significantly after verapamil, but increased significantly 1-2 h after nifedipine and felodipine. Plasma renin activity (PRA) did not change significantly with any treatment, and plasma aldosterone decreased with all three agents. ANP levels did not change significantly after verapamil, but increased significantly after nifedipine and felodipine. There was a significant positive correlation between the maximal change in ANP level and urinary sodium after nifedipine and felodipine. The increase in urinary sodium after verapamil was not significant. The role of the direct renal effect of calcium entry blockers in their persistent natriuretic action is discussed, as well as their short-term enhancement of ANP levels, which may account for the initial diuretic and natriuretic effects seen with this class of dihydropiridines.