Angiotensin II type 1 receptor blockade partially attenuates hypoxia-induced pulmonary hypertension in newborn piglets: relationship with the nitrergic system

The objective of this study was to observe possible interactions between the renin-angiotensin and nitrergic systems in chronic hypoxia-induced pulmonary hypertension in newborn piglets. Thirteen chronically instrumented newborn piglets (6.3 ± 0.9 days; 2369 ± 491 g) were randomly assigned to receive saline (placebo, P) or the AT1 receptor (AT1-R) blocker L-158,809 (L) during 6 days of hypoxia (FiO2 = 0.12). During hypoxia, pulmonary arterial pressure (Ppa; P < 0.0001), pulmonary vascular resistance (PVR; P < 0.02) and the pulmonary to systemic vascular resistance ratio (PVR/SVR; P < 0.05) were significantly attenuated in the L (N = 7) group compared to the P group (N = 6). Western blot analysis of lung proteins showed a significant decrease of endothelial NOS (eNOS) in both P and L animals, and of AT1-R in P animals during hypoxia compared to normoxic animals (C group, N = 5; P < 0.01 for all groups). AT1-R tended to decrease in L animals. Inducible NOS (iNOS) did not differ among P, L, and C animals and iNOS immunohistochemical staining in macrophages was significantly more intense in L than in P animals (P < 0.01). The vascular endothelium showed moderate or strong eNOS and AT1-R staining. Macrophages and pneumocytes showed moderate or strong iNOS and AT1-R staining, but C animals showed weak iNOS and AT1-R staining. Macrophages of L and P animals showed moderate and weak AT2-R staining, respectively, but the endothelium of all groups only showed weak staining. In conclusion, pulmonary hypertension induced by chronic hypoxia in newborn piglets is partially attenuated by AT1-R blockade. We suggest that AT1-R blockade might act through AT2-R and/or Mas receptors and the nitrergic system in the lungs of hypoxemic newborn piglets.

Increased immunohistochemical expression of YKL-40 in the spleen of patients with portal hypertension

YKL-40 has been identified as a growth factor in connective tissue cells and also a migration factor in vascular smooth muscle cells. To a large extent, the increase of serum YKL-40 is attributed to liver fibrosis and asthma. However, the relationship of the expression and clinical/prognostic significance of YKL-40 to the splenomegaly of patients with portal hypertension is unclear. In the present study, the expression of YKL-40 was studied by immunohistochemistry in 48 splenomegaly tissue samples from patients with portal hypertension and in 14 normal spleen specimens. All specimens were quickly stored at -80°C after resection. Primary antibodies YKL-40 (1:150 dilution, rabbit polyclonal IgG) and MMP-9 (1:200 dilution, rabbit monoclonal IgG) and antirabbit immunoglobulins (HRP K4010) were used in this study. The relationship of clinicopathologic features with YKL-40 is presented. The expression of YKL-40 indicated by increased immunochemical reactivity was significantly up-regulated in splenomegaly tissues compared to normal spleen tissues. Overexpression of YKL-40 was found in 68.8% of splenomegaly tissues and was significantly associated with Child-Pugh classification (P = 0.000), free portal pressure (correlation coefficient = 0.499, P < 0.01) and spleen fibrosis (correlation coefficient = 0.857, P < 0.01). Further study showed a significant correlation between YKL-40 and MMP-9 (correlation coefficient = -0.839, P < 0.01), indicating that YKL-40 might be an accelerator of spleen tissue remodeling by inhibiting the expression of MMP-9. In conclusion, YKL-40 is an important factor involved in the remodeling of spleen tissue of portal hypertension patients and can be used as a therapeutic target for splenomegaly.

Mechanisms of endothelial dysfunction in obesity-associated hypertension

Obesity is strongly associated with high blood pressure, dyslipidemia, and type 2 diabetes. These conditions synergistically increase the risk of cardiovascular events. A number of central and peripheral abnormalities can explain the development or maintenance of high blood pressure in obesity. Of great interest is endothelial dysfunction, considered to be a primary risk factor in the development of hypertension. Additional mechanisms also related to endothelial dysfunction have been proposed to mediate the development of hypertension in obese individuals. These include: increase in both peripheral vasoconstriction and renal tubular sodium reabsorption, increased sympathetic activity and overactivation of both the renin-angiotensin system and the endocannabinoid system and insulin resistance. The discovery of new mechanisms regulating metabolic and vascular function and a better understanding of how vascular function can be influenced by these systems would facilitate the development of new therapies for treatment of obesity-associated hypertension.

Correlation between sodium and potassium excretion in 24- and 12-h urine samples

Low-sodium and high-potassium diets have been recommended as an adjunct to prevention and treatment of hypertension. Analysis of these nutrients in 24-h urine has been considered the reference method to estimate daily intake of these minerals. However, 24-h urine collection is difficult in epidemiological studies, since urine must be collected and stored in job environments. Therefore, strategies for shorter durations of urine collection at home have been proposed. We have previously reported that collecting urine during a 12-h period (overnight) is more feasible and that creatinine clearance correlated strongly with that detected in 24-h samples. In the present study, we collected urine for 24 h divided into two 12-h periods (from 7:00 am to 7:00 pm and from 7:00 pm to 7:00 am next day). A sample of 109 apparently healthy volunteers aged 30 to 74 years of both genders working in a University institution was investigated. Subjects with previous myocardial infarction, stroke, renal insufficiency, and pregnant women were not included. Significant (P < 0.001) Spearman correlation coefficients (r s) were found between the total amount of sodium and potassium excreted in the urine collected at night and in the 24-h period (r s = 0.76 and 0.74, respectively). Additionally, the 12-h sodium and potassium excretions (means ± SD, 95% confidence interval) corresponded to 47.3 ± 11.2%, 95%CI = 45.3-49.3, and 39.3 ± 4.6%, 95%CI = 37.3-41.3, respectively, of the 24-h excretion of these ions. Therefore, these findings support the assumption that 12-h urine collected at night can be used as a reliable tool to estimate 24-h intake/excretion of sodium and potassium.

Acute exposure to lead increases myocardial contractility independent of hypertension development

We studied the effects of the acute administration of small doses of lead over time on hemodynamic parameters in anesthetized rats to determine if myocardial contractility changes are dependent or not on the development of hypertension. Male Wistar rats received 320 µg/kg lead acetateiv once, and their hemodynamic parameters were measured for 2 h. Cardiac contractility was evaluated in vitro using left ventricular papillary muscles as were Na+,K+-ATPase and myosin Ca2+-ATPase activities. Lead increased left- (control: 112 ± 3.7 vs lead: 129 ± 3.2 mmHg) and right-ventricular systolic pressures (control: 28 ± 1.2vs lead: 34 ± 1.2 mmHg) significantly without modifying heart rate. Papillary muscles were exposed to 8 µM lead acetate and evaluated 60 min later. Isometric contractions increased (control: 0.546 ± 0.07 vs lead: 0.608 ± 0.06 g/mg) and time to peak tension decreased (control: 268 ± 13vs lead: 227 ± 5.58 ms), but relaxation time was unchanged. Post-pause potentiation was similar between groups (n = 6 per group), suggesting no change in sarcoplasmic reticulum activity, evaluated indirectly by this protocol. After 1-h exposure to lead acetate, the papillary muscles became hyperactive in response to a β-adrenergic agonist (10 µM isoproterenol). In addition, post-rest contractions decreased, suggesting a reduction in sarcolemmal calcium influx. The heart samples treated with 8 µM lead acetate presented increased Na+,K+-ATPase (approximately 140%, P < 0.05 for control vs lead) and myosin ATPase (approximately 30%, P < 0.05 for control vs lead) activity. Our results indicated that acute exposure to low lead concentrations produces direct positive inotropic and lusitropic effects on myocardial contractility and increases the right and left ventricular systolic pressure, thus potentially contributing to the early development of hypertension.

Exaggerated blood pressure response during the exercise treadmill test as a risk factor for hypertension

Exaggerated blood pressure response (EBPR) during the exercise treadmill test (ETT) has been considered to be a risk factor for hypertension. The relationship of polymorphisms of the renin-angiotensin system gene with hypertension has not been established. Our objective was to evaluate whether EBPR during exercise is a clinical marker for hypertension. The study concerned a historical cohort of normotensive individuals. The exposed individuals were those who presented EBPR. At the end of the observation period (41.7 months = 3.5 years), the development of hypertension was analyzed within the two groups. Genetic polymorphisms and blood pressure behavior were assessed as independent variables, together with the classical risk factors for hypertension. The I/D gene polymorphism of the angiotensin-converting enzyme and M235T of angiotensinogen were ruled out as risk factors for hypertension. EBPR during ETT is not an independent influence on the chances of developing hypertension. No differences were observed between the hypertensive and normotensive individuals regarding gender (P = 0.655), skin color (P = 0.636), family history of hypertension (P = 0.225), diabetes mellitus (P = 0.285), or hypertriglyceridemia (P = 0.734). The risk of developing hypertension increased with increasing body mass index (BMI) and advancing age. The risk factors, which independently influenced the development of hypertension, were age and BMI. EBPR did not constitute an independent risk factor for hypertension and is probably a preclinical phase in the spectrum of normotension and hypertension.

Pulmonary hypertension due to acute respiratory distress syndrome

Our aims were to describe the prevalence of pulmonary hypertension in patients with acute respiratory distress syndrome (ARDS), to characterize their hemodynamic cardiopulmonary profiles, and to correlate these parameters with outcome. All consecutive patients over 16 years of age who were in the intensive care unit with a diagnosis of ARDS and an in situ pulmonary artery catheter for hemodynamic monitoring were studied. Pulmonary hypertension was diagnosed when the mean pulmonary artery pressure was >25 mmHg at rest with a pulmonary artery occlusion pressure or left atrial pressure <15 mmHg. During the study period, 30 of 402 critically ill patients (7.46%) who were admitted to the ICU fulfilled the criteria for ARDS. Of the 30 patients with ARDS, 14 met the criteria for pulmonary hypertension, a prevalence of 46.6% (95% CI; 28-66%). The most common cause of ARDS was pneumonia (56.3%). The overall mortality was 36.6% and was similar in patients with and without pulmonary hypertension. Differences in patients' hemodynamic profiles were influenced by the presence of pulmonary hypertension. The levels of positive end-expiratory pressure and peak pressure were higher in patients with pulmonary hypertension, and the PaCO2 was higher in those who died. The level of airway pressure seemed to influence the onset of pulmonary hypertension. Survival was determined by the severity of organ failure at admission to the intensive care unit.

Combined aliskiren and L-arginine treatment has antihypertensive effects and prevents vascular endothelial dysfunction in a model of renovascular hypertension

Angiotensin II is a key player in the pathogenesis of renovascular hypertension, a condition associated with endothelial dysfunction. We investigated aliskiren (ALSK) and L-arginine treatment both alone and in combination on blood pressure (BP), and vascular reactivity in aortic rings. Hypertension was induced in 40 male Wistar rats by clipping the left renal artery. Animals were divided into Sham, 2-kidney, 1-clip (2K1C) hypertension, 2K1C+ALSK (ALSK), 2K1C+L-arginine (L-arg), and 2K1C+ALSK+L-arginine (ALSK+L-arg) treatment groups. For 4 weeks, BP was monitored and endothelium-dependent and independent vasoconstriction and relaxation were assessed in aortic rings. ALSK+L-arg reduced BP and the contractile response to phenylephrine and improved acetylcholine relaxation. Endothelium removal and incubation with N-nitro-L-arginine methyl ester (L-NAME) increased the response to phenylephrine in all groups, but the effect was greater in the ALSK+L-arg group. Losartan reduced the contractile response in all groups, apocynin reduced the contractile response in the 2K1C, ALSK and ALSK+L-arg groups, and incubation with superoxide dismutase reduced the phenylephrine response in the 2K1C and ALSK groups. eNOS expression increased in the 2K1C and L-arg groups, and iNOS was increased significantly only in the 2K1C group compared with other groups. AT1 expression increased in the 2K1C compared with the Sham, ALSK and ALSK+L-arg groups, AT2 expression increased in the ALSK+L-arg group compared with the Sham and L-arg groups, and gp91phox decreased in the ALSK+L-arg group compared with the 2K1C and ALSK groups. In conclusion, combined ALSK+L-arg was effective in reducing BP and preventing endothelial dysfunction in aortic rings of 2K1C hypertensive rats. The responsible mechanisms appear to be related to the modulation of the local renin-angiotensin system, which is associated with a reduction in endothelial oxidative stress.

Effect of salt intake and potassium supplementation on brachial-ankle pulse wave velocity in Chinese subjects: an interventional study

Accumulating evidence has suggested that high salt and potassium might be associated with vascular function. The aim of this study was to investigate the effect of salt intake and potassium supplementation on brachial-ankle pulse wave velocity (PWV) in Chinese subjects. Forty-nine subjects (28-65 years of age) were selected from a rural community of northern China. All subjects were sequentially maintained on a low-salt diet for 7 days (3.0 g/day NaCl), a high-salt diet for an additional 7 days (18.0 g/day NaCl), and a high-salt diet with potassium supplementation for a final 7 days (18.0 g/day NaCl+4.5 g/day KCl). Brachial-ankle PWV was measured at baseline and on the last day of each intervention. Blood pressure levels were significantly increased from the low-salt to high-salt diet, and decreased from the high-salt diet to high-salt plus potassium supplementation. Baseline brachial-ankle PWV in salt-sensitive subjects was significantly higher than in salt-resistant subjects. There was no significant change in brachial-ankle PWV among the 3 intervention periods in salt-sensitive, salt-resistant, or total subjects. No significant correlations were found between brachial-ankle PWV and 24-h sodium and potassium excretions. Our study indicates that dietary salt intake and potassium supplementation, at least in the short term, had no significant effect on brachial-ankle PWV in Chinese subjects.

Hypertension is associated with greater heat exchange during exercise recovery in a hot environment

Individuals with systemic arterial hypertension have a higher risk of heat-related complications. Thus, the aim of this study was to examine the thermoregulatory responses of hypertensive subjects during recovery from moderate-intensity exercise performed in the heat. A total of eight essential hypertensive (H) and eight normotensive (N) male subjects (age=46.5±1.3 and 45.6±1.4 years, body mass index=25.8±0.8 and 25.6±0.6 kg/m2, mean arterial pressure=98.0±2.8 and 86.0±2.3 mmHg, respectively) rested for 30 min, performed 1 h of treadmill exercise at 50% of maximal oxygen consumption, and rested for 1 h after exercise in an environmental chamber at 38°C and 60% relative humidity. Skin and core temperatures were measured to calculate heat exchange parameters. Mean arterial pressure was higher in the hypertensive than in the normotensive subjects throughout the experiment (P<0.05, unpaired t-test). The hypertensive subjects stored less heat (H=-24.23±3.99 W·m−2vs N=-13.63±2.24 W·m−2, P=0.03, unpaired t-test), experienced greater variations in body temperature (H=-0.62±0.05°C vsN=-0.35±0.12°C, P=0.03, unpaired t-test), and had more evaporated sweat (H=-106.1±4.59 W·m−2vs N=-91.15±3.24 W·m−2, P=0.01, unpaired t-test) than the normotensive subjects during the period of recovery from exercise. In conclusion, essential hypertensive subjects showed greater sweat evaporation and increased heat dissipation and body cooling relative to normotensive subjects during recovery from moderate-intensity exercise performed in hot conditions.

Risk factors for pulmonary hypertension in patients receiving maintenance peritoneal dialysis

We investigated the risk factors for pulmonary hypertension (PH) in patients receiving maintenance peritoneal dialysis (MPD). A group of 180 end-stage renal disease patients (124 men and 56 women; mean age: 56.43±8.36) were enrolled in our study, which was conducted between January 2009 and June 2014. All of the patients received MPD treatment in the Dialysis Center of the Second Affiliated Hospital of Soochow University. Clinical data, laboratory indices, and echocardiographic data from these patients were collected, and follow-ups were scheduled bi-monthly. The incidence and relevant risk factors of PH were analyzed. The differences in measurement data were compared by t-test and enumeration data were compared with the χ2 test. Among the 180 patients receiving MPD, 60 were diagnosed with PH. The remaining 120 were regarded as the non-PH group. Significant differences were observed in the clinical data, laboratory indices, and echocardiographic data between the PH and non-PH patients (all P<0.05). Furthermore, hypertensive nephropathy patients on MPD showed a significantly higher incidence of PH compared with non-hypertensive nephropathy patients (P<0.05). Logistic regression analysis showed that the proportion of internal arteriovenous fistula, C-reactive protein levels, and ejection fraction were the highest risk factors for PH in patients receiving MPD. Our study shows that there is a high incidence of PH in patients receiving MPD and hypertensive nephropathy patients have an increased susceptibility to PH.

Histidine-tryptophan-ketoglutarate solution decreases mortality and morbidity in high-risk patients with severe pulmonary arterial hypertension associated with complex congenital heart disease: an 11-year experience from a single institution

Cardioplegic reperfusion during a long term ischemic period interrupts cardiac surgery and also increases cellular edema due to repeated solution administration. We reviewed the clinical experiences on myocardial protection of a single perfusion with histidine-tryptophan-ketoglutarate (HTK) for high-risk patients with severe pulmonary arterial hypertension associated with complex congenital heart disease. This retrospective study included 101 high-risk patients undergoing arterial switch operation between March 2001 and July 2012. We divided the cohort into two groups: HTK group, myocardial protection was carried out with one single perfusion with HTK solution; and St group, myocardial protection with conventional St. Thomas' crystalloid cardioplegic solution. The duration of cardiopulmonary bypass did not differ between the two groups. The mortality, morbidity, ICU stay, post-operative hospitalization time, and number of transfusions in HTK group were lower than those in St group (P<0.05). Univariate and multivariate analysis showed that HTK is a statistically significant independent predictor of decreased early mortality and morbidity (P<0.05). In conclusion, HTK solution seems to be an effective and safe alternative to St. Thomas' solution for cardioplegic reperfusion in high-risk patients with complex congenital heart disease.

Acid and salt uptake during the marinatig process of Engraulis anchoita fillets influence of the solution: fish ratio and agitation

The aims of this research were to determine the effect of different conditions of the marination stage on the salt and acid uptake, immersion time, and sensorial characteristics during the marinating process of anchovy (Engraulis anchoita). Different solution:fish ratios and the agitation effect during this stage were analyzed. The ratios used were: 0.77:1, 3:1 and 10:1 (with and without agitation). An increase of marinating solution:fish ratio causes a higher speed of acid and salt penetration The product obtained with the 10:1 ratio had a dry and fibrous texture and a slightly salty taste. Salt concentration was statistically significantly lower (p < 0.01) in the samples with agitation. Agitation did not influence the acid uptake, and the salt penetration speed decreased, but rancidity was detected in this product. The ratio 3:1 decreases the marinating time without damaging sensory attributes and can be used in the fish marinating process.

Saline distribution during multicomponent salting in pre-cooked quail eggs

The relationship of NaCl with problems of arterial hypertension has led to a reduction in the levels of this salt in food production. KCl has been used as a partial substitute for NaCl since it cannot be completely substituted without affecting the acceptability of the end product. In this study, the diffusion that occurs during quail egg salting in static and stirred brine was simulated. The mathematical model used was based on a generalization of the Fick's 2nd law, and the COMSOL Multiphysics software was used to simulate the diffusion in the NaCl-KCl-water system. The deviations in the simulated data and experimental data were 2.50% for NaCl and 6.98% for KCl in static brine, while in the stirred brine they were 3.48% for NaCl and 4.72% for KCl. The simulation results presented good agreement with the experimental values and validated the predictive capacity of the model.

Chemical, biochemical, and microbiological aspects of chitosan quaternary salt as active coating on sliced apples

The biocompatibility of chitosan and chitosan quaternary salt coatings was evaluated for use as edible coatings for sliced apple. Measurement of water loss, color change, and fungal growth appearance were monitored as a function of time. A significant brownish effect was observed on chitosan coated slices, varying greatly from L* = 76.5 and Hue angle = 95.9° (t = 0) to L* = 45.3 and Hue angle = 69.8° (t = 3 days), whilst for TMC coated samples the variation was considerable lower (L* = 74.1; Hue angle = 95.0°) to (L* = 67.0; Hue angle = 83.8°) within the same period. The hydrosoluble derivative N,N,N-trimethylchitosan demonstrated good antifungal activity against P. expansum although highly dependent on the polymer properties such as degree of quaternization. The most efficient formulation was that prepared from derivative having a degree of quaternization of 45%, high solubility, and high viscosity. This formulation restrained fungus spreading up to 30%, while for the control it reached almost 80% of the total assessed surfaces during 7 days of storage.