Urinary Potassium Excretion, Fibroblast Growth Factor 23, and Incident Hypertension in the General Population-Based PREVEND Cohort.

High plasma fibroblast growth factor 23 (FGF23) and low potassium intake have each been associated with incident hypertension. We recently demonstrated that potassium supplementation reduces FGF23 levels in pre-hypertensive individuals. The aim of the current study was to address whether 24-h urinary potassium excretion, reflecting dietary potassium intake, is associated with FGF23, and whether FGF23 mediates the association between urinary potassium excretion and incident hypertension in the general population. At baseline, 4194 community-dwelling individuals without hypertension were included. Mean urinary potassium excretion was 76 (23) mmol/24 h in men, and 64 (20) mmol/24 h in women. Plasma C-terminal FGF23 was 64.5 (54.2-77.8) RU/mL in men, and 70.3 (56.5-89.5) RU/mL in women. Urinary potassium excretion was inversely associated with FGF23, independent of age, sex, urinary sodium excretion, bone and mineral parameters, inflammation, and iron status (St. ß -0.02, p < 0.05). The lowest sex-specific urinary potassium excretion tertile (HR 1.18 (95% CI 1.01-1.37)), and the highest sex-specific tertile of FGF23 (HR 1.17 (95% CI 1.01-1.37)) were each associated with incident hypertension, compared with the reference tertile. FGF23 did not mediate the association between urinary potassium excretion and incident hypertension. Increasing potassium intake, and reducing plasma FGF23 could be independent targets to reduce the risk of hypertension in the general population.

Short-Term Supplemental Dietary Potassium from Potato and Potassium Gluconate: Effect on Calcium Retention and Urinary pH in Pre-Hypertensive-to-Hypertensive Adults.

Potassium supplementation has been associated with reduced urinary calcium (Ca) excretion and increased Ca balance. Dietary interventions assessing the impact of potassium on bone are lacking. In this secondary analysis of a study designed primarily to determine blood pressure effects, we assessed the effects of potassium intake from potato sources and a potassium supplement on urinary Ca, urine pH, and Ca balance. Thirty men (n = 15) and women (n = 15) with a mean ± SD age and BMI of 48.2 ± 15 years and 31.4 ± 6.1 kg/m2, respectively, were enrolled in a cross-over, randomized control feeding trial. Participants were assigned to a random order of four 16-day dietary potassium interventions including a basal diet (control) of 2300 mg/day (~60 mmol/day) of potassium, and three phases of an additional 1000 mg/day (3300 mg/day(~85 mmol/day) total) of potassium in the form of potatoes (baked, boiled, or pan-heated), French fries (FF), or a potassium (K)-gluconate supplement. Calcium intake for all diets was approximately 700-800 mg/day. Using a mixed model ANOVA there was a significantly lower urinary Ca excretion in the K-gluconate phase (96 ± 10 mg/day) compared to the control (115 ± 10 mg/day; p = 0.027) and potato (114 ± 10 mg/day; p = 0.033). In addition, there was a significant difference in urinary pH between the supplement and control phases (6.54 ± 0.16 vs. 6.08 ± 0.18; p = 0.0036). There were no significant differences in Ca retention. An increased potassium intake via K-gluconate supplementation may favorably influence urinary Ca excretion and urine pH. This trial was registered at ClinicalTrials.gov as NCT02697708.

Heat-sensitive moxibustion self-administration in patients in the community with primary hypertension: A protocol for a multi-center, pragmatic, non-randomized trial.

BACKGROUND: Although the efficacy of antihypertensive drugs has been well established for primary hypertension, their effectiveness is always limited by side effects and poor compliance. Heat-sensitive moxibustion is an innovative acupoint stimulation therapy that is promising as a community health care intervention for hypertension. AIMS: This study aims to evaluate the pragmatic effectiveness and safety of heat-sensitive moxibustion self-administration by patients in the community with primary hypertension. METHODS: This study will adopt a multi-center, pragmatic, nonrandomized design. Six hundred patients with primary hypertension will be recruited from 4 communities. Each patient will choose to either receive heat-sensitive moxibustion self-administration + original antihypertensive drugs or maintain their original antihypertensive drugs without heat-sensitive moxibustion for 1 year. EXPECTED OUTCOMES: The primary outcome will be changes in systolic and diastolic blood pressures and the percentage changes in the doses of antihypertensive drugs. The secondary outcomes will be changes in quality of life assessed by a validated patient-reported outcome scale and the levels of fasting blood glucose, glycated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, urinary albumin, and serum creatinine. The proportion of patients with poor compliance with the heat-sensitive moxibustion regimen will also be evaluated as a secondary outcome. The safety of heat-sensitive moxibustion will be considered by analyzing the incidence of all and serious adverse events and their correlation with heat-sensitive moxibustion. DISCUSSION: The findings of this study will provide pragmatic evidence for heat-sensitive moxibustion self-administration in patients in the community with primary hypertension and may also establish an ethical basis for further randomized controlled trials. TRIAL REGISTRATION: The protocol of this trial was registered in ClinicalTrials.gov at May 11, 2020 (No. NCT04381520).

Impact of mineralocorticoid receptor blockade with direct renin inhibition in angiotensin II-dependent hypertensive mice.

It has been suggested that aldosterone breakthrough during treatment with a type 1 angiotensin II receptor (AT1R) blocker (ARB) may be an important risk factor for the progression of renal and cardiovascular disease. We examined whether the direct renin inhibitor, aliskiren caused aldosterone breakthrough in angiotensin II (Ang II)-dependent hypertensive mice. The effect of combination therapy with aliskiren and eplerenone was compared with that of therapy using renin-angiotensin system (RAS) blockade. Tsukuba hypertensive mice were treated for 12 weeks with aliskiren (30 mg/kg/day, i.p), candesartan (5 mg/kg/day, p.o), eplerenone (100 mg/kg/day, p.o) aliskiren and candesartan, aliskiren and eplerenone or candesartan and eplerenone. Blood pressure, urinary aldosterone and angiotensinogen (AGTN) excretion; plasma endothelin-1 concentration; kidney weight; urinary albumin excretion (UAE); glomerular injury; and renal messenger RNA (mRNA) levels for transforming growth factor (TGF)-ß1, plasminogen activator inhibitor (PAI)-1, angiotensin-converting enzyme (ACE) and AT1R were measured. Combination therapy with aliskiren and candesartan caused a further decrease in blood pressure (p < 0.05) compared with either agent alone. Urinary aldosterone excretion was decreased significantly by 4 weeks of treatment with aliskiren or candesartan (p < 0.05). However, it was increased again by treatment with candesartan or aliskiren for 12 weeks. Combination therapy with aliskiren and eplerenone significantly decreased UAE, the glomerulosclerosis index, and PAI-1 and TGF-ß1 mRNA levels compared with all other therapies (p < 0.05). Treatment with aliskiren decreased urinary aldosterone excretion at 4 weeks and increased it at 12 weeks. Combination therapy with a direct renin inhibitor and a mineralocorticoid receptor blocker may be effective for the prevention of renal injury in Ang II-dependent hypertension.

Cardioprotective Effects of the Novel Compound Vastiras in a Preclinical Model of End-Organ Damage.

Cardiac hypertrophy and renal damage associated with hypertension are independent predictors of morbidity and mortality. In a model of hypertensive heart disease and renal damage, we tested the actions of continuous administration of Vastiras, a novel compound derived from the linear fragment of ANP (atrial natriuretic peptide), namely pro-ANP31-67, on blood pressure and associated renal and cardiac function and remodeling. Of note, this peptide, unlike the ring structured forms, does not bind to the classic natriuretic peptide receptors. Dahl/Salt-Sensitive rats fed a 4% NaCl diet for 6 weeks developed hypertension, cardiac hypertrophy, and renal damage. Four weeks of treatment with 50 to 100 ng/kg per day of Vastiras exhibited positive effects on renal function, independent of blood pressure regulation. Treated rats had increased urine excretion, natriuresis, and enhanced glomerular filtration rate. Importantly, these favorable renal effects were accompanied by improved cardiac structure and function, including attenuated cardiac hypertrophy, as indicated by decreased heart weight to body weight ratio, relative wall thickness, and left atrial diameter, as well as reduced fibrosis and normalized ratio of the diastolic mitral inflow E wave to A wave. A renal subtherapeutic dose of Vastiras (25 ng/kg per day) induced similar protective effects on the heart. At the cellular level, cardiomyocyte size and t-tubule density were preserved in Vastiras-treated compared with untreated animals. In conclusion, these data demonstrate the cardiorenal protective actions of chronic supplementation of a first-in-class compound, Vastiras, in a preclinical model of maladaptive cardiac hypertrophy and renal damage induced by hypertension.

Quantifying adherence to antihypertensive medication for chronic hypertension during pregnancy.

Estimates of adherence to antihypertensive treatment in pregnancy are limited; identifying non-adherence could facilitate intervention and optimise blood pressure control. This study aimed to evaluate adherence to antihypertensive treatment amongst pregnant women with chronic hypertension using high-performance liquid chromatography-tandem mass spectrometry instrumentation. Spot urine samples collected from women who were randomised to labetalol or nifedipine were assessed. Samples from 74 women were included; documented prescribing and urine metabolite detection were concordant in 88% (n = 65). Evidence of self-administration of alternative treatment was observed in 8% (n = 6). Measurement of urinary antihypertensive metabolites in pregnancy provides insight into treatment adherence.

The Percentage of Dietary Phosphorus Excreted in the Urine Varies by Dietary Pattern in a Randomized Feeding Study in Adults.

BACKGROUND: Urinary phosphorus excretion has been proposed as a recovery biomarker of dietary phosphorus intake. However, it is unclear whether phosphorus excretion is constant across a range of dietary and nondietary factors. OBJECTIVE: We assessed whether percentage urinary phosphorus excretion is constant across 3 dietary patterns in the Dietary Approaches to Stop Hypertension (DASH) trial. METHODS: DASH is a completed feeding study of 459 prehypertensive and stage 1 hypertensive adults (52% male, 56% black). After a 3-wk run-in on a typical American (control) diet, participants were randomly assigned to the control diet, a diet rich in fruits and vegetables (FV diet), or a diet rich in fruits, vegetables, and low-fat dairy with reduced saturated fat and cholesterol (DASH diet) for 8 wk. We estimated the percentage phosphorus excretion as urinary phosphorus excretion (from 24 h urine) divided by phosphorus intake (from analyzed food composites). Differences between group means for all 3 diets were compared by ANOVA followed by pairwise comparisons with Tukey's honest significant difference test. RESULTS: At the end of the intervention, the mean phosphorus intake was 1176 mg/d (95% CI: 1119, 1233 mg/d), 1408 mg/d (1352, 1464 mg/d), and 2051 mg/d (1994, 2107 mg/d) in the control, FV, and DASH diet, respectively (P < 0.001, all comparisons). The mean phosphorus excretion was 734 mg/d (682, 787 mg/d), 705 mg/d (654, 756 mg/d), and 872 mg/d (820, 923 mg/d) in the control, FV, and DASH diet, respectively (P = 0.74 control vs. FV, P < 0.001 all other comparisons). The mean percentage phosphorus excretion was 63% (60%, 67%), 51% (48%, 54%), and 43% (39%, 46%) in the control, FV, and DASH diet, respectively (P < 0.001, all comparisons). CONCLUSIONS: These findings in prehypertensive and stage 1 hypertensive adults strongly suggest that urinary phosphorus excretion should not be used as a recovery biomarker for dietary phosphorus intake, given the wide range of urinary phosphorus excretion across dietary patterns. This trial is registered at clinicaltrials.gov as NCT0000054.

Urine Haptoglobin and Haptoglobin-Related Protein Predict Response to Spironolactone in Patients With Resistant Hypertension.

Resistant hypertension prevalence is progressively increasing, and prolonged exposure to suboptimal blood pressure control results in higher cardiovascular risk and end-organ damage. Among various antihypertensive agents, spironolactone seems the most effective choice to treat resistant hypertension once triple therapy including a diuretic fails. However success in blood pressure control is not guaranteed, adverse effects are not negligible, and no clinical tools are available to predict patient's response. Complementary to our previous study of resistant hypertension metabolism, here we investigated urinary proteome changes with potential capacity to predict response to spironolactone. Twenty-nine resistant hypertensives were included. A prospective study was conducted and basal urine was collected before spironolactone administration. Patients were classified in responders or nonresponders in terms of blood pressure control. Protein quantitation was performed by liquid chromatography-mass spectrometry; ELISA and target mass spectrometry analysis were performed for confirmation. Among 3310 identified proteins, HP (haptoglobin) and HPR (haptoglobin-related protein) showed the most significant variations, with increased levels in nonresponders compared with responders before drug administration (variation rate, 5.98 and 7.83, respectively). Protein-coordinated responses were also evaluated by functional enrichment analysis, finding oxidative stress, chronic inflammatory response, blood coagulation, complement activation, and regulation of focal adhesions as physiopathological mechanisms in resistant hypertension. In conclusion, protein changes able to predict patients' response to spironolactone in basal urine were here identified for the first time. These data, once further confirmed, will support clinical decisions on patients' management while contributing to optimize the rate of control of resistant hypertensives with spironolactone.

Effects of Different Doses of Irbesartan Combined With Spironolactone on Urinary Albumin Excretion Rate in Elderly Patients With Early Type 2 Diabetic Nephropathy.

BACKGROUND: There is a lack of research on the effect of low dose of angiotensin receptor blockers combined with spironolactone, and the effect of high dose of angiotensin receptor blockers alone on the urinary albumin excretion rate (UAER) in elderly patients with early type 2 diabetic nephropathy (DN). METHODS: We conducted a prospective, randomized, open-label, parallel-controlled study that included 244 elderly patients with early DN and mild-to-moderate essential hypertension. Patients were randomly divided into 4 groups: low-dose irbesartan (group A), high-dose irbesartan (group B), low-dose irbesartan combined with spironolactone (group C) and high-dose irbesartan combined with spironolactone (group D). Changes in UAER, serum potassium and blood pressure were compared. RESULTS: There were no statistical differences in the baseline characteristics among groups. Furthermore, no significant difference in blood pressure before and after treatment was found among different groups. After 72-week treatment, UAER in group D was lower compared to group A and B (P < 0.05). Meanwhile, compared with group B, UAER in group C decreased significantly (P < 0.05). Additionally, significantly higher serum potassium was found in group D compared to other groups (P < 0.05). Also, group D had the highest count of patients who withdrew from the study due to hyperkalemia compared to other groups (P < 0.05). CONCLUSIONS: Our results indicate high-dose irbesartan combined with spironolactone may be more efficient in reducing UAER in elderly patients with early DN, but this treatment could cause hyperkalemia. Low-dose irbesartan combined with spironolactone was shown to be safer and more effective in decreasing UAER compared to high-dose irbesartan.

The acute diuretic effect of an ethanolic fraction of Phyllanthus amarus (Euphorbiaceae) in rats involves prostaglandins.

BACKGROUND: Phyllanthus amarus (Schum & Thonn), a plant belonging to the family of Euphorbiaceae is used in Ivorian traditional medicine to treat cardiovascular disorders such as hypertension. However, although this plant has been described as a diuretic agent, the underlying mechanism remains unclear. Therefore, the aim of the present study was to investigate the mechanism action of diuretic effects of an ethanolic fraction of Phyllanthus amarus (EFPA) in rats. METHODS: Effects of EFPA on urinary excretion were carried out for doses ranging from 5 to 80 mg/kg given by intraperitoneal injection (i.p.) and compared with that induced by furosemide (5 mg/kg) after 8 h. Thereafter, the diuretic activity of EFPA was also evaluated in the presence of indomethacin (5 mg/kg, i.p.) in order to determine the involvement of prostaglandins, after 24 h. RESULTS: Between 5 and 80 mg/kg, EFPA induced a significant urinary excretion. The profile of urinary excretion showed that after 2 h, the highest dose of 80 mg/kg induced a urinary volumetric excretion (UVE), which was similar to that induced by furosemide. After 24 h, EFPA at 10 mg/kg increased significantly UVE, Na+ (43 mEq) and Cl¯ (97 mEq) urinary excretions without promoting kaliuresis. In rats pretreated with indomethacin, the urinary excretion and the natriuretic response of EFPA were significantly reduced. CONCLUSION: Altogether, this study has shown that EFPA promotes a significant urinary excretion of water and Na+, confirming its diuretic activity. Moreover, the increased diuresis could be attributed, at least in part, to the involvement of prostaglandins.

Comparison of the Effects of Three Tea Cultivars (Camellia sinensis L.) on Nitric Oxide Production and Aortic Soluble Guanylate Cyclase Expression in High-Salt Diet-Fed Spontaneously Hypertensive Rats.

Studies have suggested that the consumption of green tea reduces the risk of cardiovascular diseases. Although epigallocatechin gallate (EGCG) is the best studied active substance characteristic of green tea, previous results on EGCG do not appear sufficient to explain completely the mechanism of cardiovascular protection by green tea. Therefore, we investigated the effect of three different tea cultivars, "Yabukita," "Sofu," and "Sunrouge," which have characteristic flavonoid compositions, on the nitric oxide (NO) production and the related protein expression in the aorta of spontaneously hypertensive rats (SHRs) fed a high-salt diet. As a result, the reduction of urinary NO metabolite (NOx) levels, which reflect whole-body NO production, caused by the high-salt diet were significantly prevented by all three tea infusions. The improvement of NOx reduction in the tea-intake groups was unlikely to be caused by the changes in oxidative damage. On the other hand, as a partial effect, only "Yabukita" or "Sofu" increased the expression of the soluble guanylate cyclase, a receptor for NO, in the thoracic aorta. In the present study, the differences in the composition of these three cultivars led to partially different effects on NO signaling in SHRs, suggesting the physiological significance of subdominant ingredients besides EGCG.

Urine fibroblast growth factor 23 levels in hypertensive children and adolescents.

AIM: To determine the correlation of urinary fibroblast growth factor 23 (FGF23) excretion with blood pressure and calcium-phosphorus metabolism. METHODS: The study included 42 hypertensive (17 girls) and 46 healthy children and adolescents (17 girls) aged 6-18 years admitted to the Department of Pediatrics and Nephrology, Medical University of Bialystok between January 2013 and December 2013. FGF23 in urine was measured using Human Intact FGF-23 ELISA Kit. RESULTS: Hypertensive participants had significantly higher urine FGF23/creatinine values than the reference group (8.65 vs 5.59 RU/mg creatinine, P=0.007). Urine FGF23/creatinine positively correlated with systolic blood pressure in all participants. In hypertensive patients, urine FGF23/creatinine positively correlated with serum calcium and negatively with serum 25(OH)D, urinary calcium, phosphorus, and magnesium. CONCLUSION: This study found that FGF23 may play an important role in the pathogenesis of hypertension in children and adolescents, but our results should be confirmed by further studies.

Effects of sodium and potassium supplementation on blood pressure and arterial stiffness: a fully controlled dietary intervention study.

We performed a randomised, placebo-controlled, crossover study to examine the effects of sodium and potassium supplementation on blood pressure (BP) and arterial stiffness in untreated (pre)hypertensive individuals. During the study, subjects were on a fully controlled diet that was relatively low in sodium and potassium. After a 1-week run-in period, subjects received capsules with supplemental sodium (3 g d(-1), equals 7.6 g d(-1) of salt), supplemental potassium (3 g d(-1)) or placebo, for 4 weeks each, in random order. Fasting office BP, 24-h ambulatory BP and measures of arterial stiffness were assessed at baseline and every 4 weeks. Of 37 randomized subjects, 36 completed the study. They had a mean pre-treatment BP of 145/81 mm Hg and 69% had systolic BP ⩾140 mm Hg. Sodium excretion was increased by 98 mmol per 24 h and potassium excretion by 63 mmol per 24 h during active interventions, compared with placebo. During sodium supplementation, office BP was significantly increased by 7.5/3.3 mm Hg, 24-h BP by 7.5/2.7 mm Hg and central BP by 8.5/3.6 mm Hg. During potassium supplementation, 24-h BP was significantly reduced by 3.9/1.6 mm Hg and central pulse pressure by 2.9 mm Hg. Pulse wave velocity and augmentation index were not significantly affected by sodium or potassium supplementation. In conclusion, increasing the intake of sodium caused a substantial increase in BP in subjects with untreated elevated BP. Increased potassium intake, on top of a relatively low-sodium diet, had a beneficial effect on BP. Arterial stiffness did not materially change during 4-week interventions with sodium or potassium.

Efficacy and safety of combination therapy of high-dose losartan and hydrochlorothiazide in patients with hypertension.

OBJECTIVE: We analyzed the efficacy and safety of combination therapy of high-dose losartan (100 mg/day) and hydrochlorothiazide (HCTZ, 12.5 mg/day) compared with those of the combination of high-dose telmisartan (80 mg/day) and HCTZ (12.5 mg/day). METHODS: Forty hypertensive patients who received a combination of high-dose telmisartan and HCTZ were enrolled. We applied a changeover strategy with switching from a combination of high-dose telmisartan and HCTZ to high-dose losartan and HCTZ. We divided the patients into two groups; those who achieved the target blood pressure (controlled group) and those who did not reach the target blood pressure (uncontrolled group) before the changeover and performed further analysis. RESULTS: The uncontrolled group showed a significant decrease in systolic blood pressure (SBP) (143±12 mmHg to 126±11 mmHg at three months). In addition, serum uric acid significantly decreased in all subjects, and in each of the controlled and uncontrolled groups. There were no significant changes in other biochemical parameters, such as potassium and hemoglobin A1c, at three months after the changeover in all subjects. CONCLUSION: Combination therapy with high-dose losartan and HCTZ was superior to the combination of telmisartan and HCTZ with respect to significant decreases in systolic blood pressure and serum uric acid in hypertensive patients.

Effects of the T/L-type calcium channel blocker benidipine on albuminuria and plasma aldosterone concentration. A pilot study involving switching from L-type calcium channel blockers to benidipine.

Albuminuria and a high plasma aldosterone concentration (PAC) are prognosis factors predicting a poor outcome for cardiovascular disease. We examined here the effects of benidipine, a T/L-type calcium channel blocker (CCB), on albuminuria and PAC.Thirty-one patients with essential hypertension who received an L-type CCB and achieved the target blood pressure (BP) indicated by the Treatment Guidelines of the Japan Society of Hypertension (JSH2009) were investigated. The Ltype CCB under treatment was switched to benidipine at a dose in which equivalent BP reduction was expected. BP and estimated glomerular filtration rate at 6 months after switching to benidipine were not significantly different from those at baseline. The urinary-albumin-creatinine ratio (UACR) decreased significantly by 36.9% (P = 0.001). No significant change was observed in plasma renin activity (P = 0.063). The PAC of all patients decreased significantly by 11.8% (P = 0.002). When analyzed by daily doses of benidipine, the PAC appeared to have decreased in patients who received 4 mg per day of benidipine (n = 14), although statistical significance was not reached (P = 0.096). The PAC in patients who received 8 mg per day of benidipine (n =17) was significantly reduced by 13.2% (P = 0.017).In hypertensive patients whose BP is controlled by L-type CCB, switching to the T/L-type CCB benidipine maintained BP control and reduced UACR. In addition, the high dose of benidipine reduced the PAC independent of BP control. These results suggest the T/L-type CCB benidipine may contribute to cardio-renal protection in addition to lowering BP.

Effect of salt intake and potassium supplementation on serum renalase levels in Chinese adults: a randomized trial.

Renalase, a recently discovered enzyme released by the kidneys, breaks down blood-borne catecholamines and may thus regulate blood pressure (BP). Animal studies have suggested that high levels of dietary salt might reduce blood and kidney renalase levels. We conducted a randomized trial to assess the effects of altered salt and potassium intake on serum renalase levels and the relationship between serum renalase levels and BP in humans.Forty-two 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 of NaCl), a high-salt diet for additional 7 days (18.0 g/day of NaCl), and a high-salt diet with potassium supplementation for final 7 days (18.0 g/day of NaCl + 4.5 g/day of KCl).Serum renalase levels were significantly higher than baseline levels during the low-salt diet intervention period. Renalase levels decreased with the change from the low-salt to high-salt diet, whereas dietary potassium prevented the decrease in serum renalase induced by the high-salt diet. There was a significant inverse correlation between the serum renalase level and 24-h urinary sodium excretion. No significant correlation was found between the renalase level and BP among the different dietary interventions.The present study indicates that variations in dietary salt intake and potassium supplementation affect the serum renalase concentration in Chinese subjects.

Effects of Tulbaghia violacea Harv. (Alliaceae) rhizome methanolic extract on kidney function and morphology in Dahl salt-sensitive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Tulbaghia violacea has been used traditionally for the treatment of several ailments, including hypertension. The herb has been shown to have antihypertensive properties which have been attributed to its angiotensin-converting enzymeinhibitory (ACEI) activity. It could, therefore, prove beneficial in ameliorating renal pathology associated with hypertension. To evaluate the effects of long-term administration of Tulbaghia violacea on renal function and morphology in the Dahl salt-sensitive (DSS) rat model. MATERIALS AND METHODS: Male DSS rats were treated intra-peritoneally (i.p.) as follows: methanolic extract of Tulbaghia violacea: (TVL) (50 mg/kg/b.w.), captopril: (CAP) (25 mg/kg/b.w.), or distilled water, control: (CON) (3 ml/kg/b.w.). Blood pressure (BP) was measured bi-weekly, whilst 24-h urine volumes and electrolyte concentrations were assessed weekly. Animals were sacrificed on day 49 by halothane overdose. Blood was removed for determination of plasma and serum electrolytes. Left kidney tissues were harvested for the determination of nuclear factor-kappaß (NF-kß) and transforming growth factor-ß (TGF-ß) gene expressions. RESULTS: TVL significantly reduced mean arterial pressure (MAP) and diastolic blood pressure (DBP). TVL showed reduced blood urea nitrogen, serum creatinine, total protein in urine as well as increased serum total protein. TVL decreased thiobarbituric acid reactive substances (TBARS) and increased glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity and nitric oxide significantly. NF-kß and TGF-ß) gene expressions were significantly reduced in TVL and CAP treated rats. Moreover, renal morphology improved significantly in TVL and CAP treated animals. CONCLUSION: TVL and CAP demonstrated marked improvement in renal function and morphology.

Interaction between essential elements selenium and zinc with cadmium and mercury in samples from hypertensive patients.

The abnormal metabolism of metal ions plays an important role in health and disease conditions; hence, the studies about them have received much interest. The objective of this study was to evaluate the association between trace and toxic elements zinc (Zn), cadmium (Cd), selenium (Se), and mercury (Hg) in biological samples (scalp hair, blood, and urine) of hypertensive patients (n = 257), residents of Hyderabad, Pakistan. For comparison purpose, the biological samples of age-matched healthy controls were selected as referents. The concentrations of trace and toxic elements were measured by atomic absorption spectrophotometer prior to microwave-assisted acid digestion. The validity and accuracy of the methodology was checked using certified reference materials and by the conventional wet acid digestion method. The recovery of all studied elements was found in the range of 96.4-99.1 % in certified reference materials. The results of this study showed that the mean values of Cd and Hg were significantly higher in scalp hair, blood, and urine samples of hypertensive patients than in referents (P < 0.001), whilst the concentrations of Zn and Se were lower in the scalp hair and blood, but higher in the urine samples of hypertensive patients. The deficiency of Zn and Se and the high exposure of toxic metals may be synergistic with risk factors associated with hypertension.