Blood Pressure Lowering Properties Research Articles

Safety, tolerability and blood pressure lowering of the innovative guanylyl cyclase a-receptor activator MANP in an ethnically diverse resistant hypertension population: a phase 1B clinical trial

Abstract Background/Introduction MANP is a novel atrial natriuretic peptide (ANP) analog bioengineered as a particulate guanylyl cyclase A receptor (GC-A) activator with superior receptor binding, resistance to neprilysin degradation, natriuretic, aldosterone suppressing and blood pressure (BP) lowering properties than native ANP. MANP is now under clinical development for resistant hypertension (RH). The rationale for its design was the fundamental role of the ANP/GC-A system in BP homeostasis through which GC-A activation with MANP leads to BP reduction through renal, vascular, and hormonal mechanisms mediated by the second messenger cGMP. Purpose We investigated the safety, tolerability, cGMP activation and BP reductions of MANP compared to placebo in subjects with RH. Methods We performed a double-blind, placebo controlled randomized trial in 36 RH patients comprised of approximately 50% non-African Americans (NAA) and 50% AA. MANP was administered in 6 cohorts receiving ascending subcutaneous (SQ) doses of MANP once daily from 3 ug/kg to a maximal dose of 7 ug/kg or placebo for 5 days and then followed for 21 days after dosing. Endpoints included safety, cGMP activation and changes in systolic BP (SBP), aldosterone (Aldo) levels and glomerular filtration rate (GFR). Results MANP was safe and well tolerated. One patient in the 7 ug/kg cohort was discontinued due to symptomatic hypotension. Compared to baseline, plasma cGMP increased in all MANP groups on Day 1 and Day 5 with no change in the placebo group. The maximal SBP reduction in the MANP group on Days 1 (D1) and 5 (D5) was -17.5 (D1) and -16 mmHg (D5) with 3 ug/kg (lowest dose) and -39.5 (D1) and -36.3 mmHg (D5) with 7 ug/kg (highest dose); Changes in the Placebo group were -6.3 (D1) and -16.7 mmHg (D5). Notably, the SBP reductions in AA were greater than NAA in the 4 and 7 ug/kg cohorts. After the 1-hour timepoint on both the first and fifth days, Aldo and percentage of Aldo reduction generally remained suppressed compared to baseline. Twenty-one days after MANP dosing, SBP remained lower in three groups receiving SQ MANP (4, 4.5 and 7 ug/kg) compared to placebo in association with a preservation of GFR. There were no reported drug related serious adverse events. Conclusions This clinical trial demonstrates that once a day SQ administration of MANP in RH subjects activates cGMP, without attenuation over 5 days, and reduces SBP and preserves GFR. At higher doses of MANP, SBP reductions were greater in AA compared to NAA. MANP also demonstrated Aldo inhibiting actions compared to placebo. Importantly, MANP was overall safe and well-tolerated. Our findings support the continued clinical development of MANP as a novel GC-A activating peptide for the treatment of RH.

The blood pressure-lowering property of subcutaneous semaglutide: a systematic review, meta-analysis, and meta-regression.

Semaglutide is a glucagon-like peptide (GLP1) receptor agonist with unprecedented weight-lowering and anti-hyperglycemic properties. Recent clinical trials reported that subcutaneous semaglutide can modulate blood pressure; however, its effect on blood pressure widely varied in different studies and different subgroups of patients. PubMed, Web of Science, Scopus, and the Cochrane Library were systematically searched from the inception to July 18, 2024. Due to high heterogeneity, a random-effects model was adopted to pool data. Twenty clinical trials with 15,312 participants in the placebo group and 18,231 participants in the semaglutide group were included in this study. Subcutaneous semaglutide significantly decreased both systolic (WMD - 3.71 mmHg, 95% CI (-4.29, -3.13), I2: 50.2%) and diastolic (WMD - 1.10 mmHg, 95% CI (-1.58, -0.63), I2: 69.7%) blood pressure. Subgroup analyses indicated that the blood pressure-lowering property of subcutaneous semaglutide was greater among patients without diabetes, with lower baseline hemoglobin A1c (HbA1c), baseline body mass index (BMI) greater than 35kg/m2, dose of semaglutide more than 1mg/week, baseline systolic blood pressure equal or less than 130 mmHg, weight loss greater than 10kg, and BMI reduction greater than 3kg/m2. In addition, a treatment length of 50 to 100 weeks was associated with greater blood pressure-lowering effects in subgroup analysis. After adjusting for other factors, meta-regression revealed that placebo-adjusted weight change was independently correlated with the effect of semaglutide on systolic and diastolic blood pressure. Subcutaneous semaglutide can significantly decrease systolic and diastolic blood pressure, particularly in selected groups of patients.

Antihypertensive effects of SGLT2 inhibitors; a letter to the editor on new concepts

SGLT2 inhibitors, primarily used to treat diabetes, have shown potential antihypertensive effects by reducing blood pressure through mechanisms like natriuresis, diuresis, and weight loss. These medications may also improve arterial stiffness and reduce inflammation, impacting to their blood pressure-lowering properties.

Differing contributions of the gut microbiota to the blood pressure lowering effects induced by first-line antihypertensive drugs.

This study analyses whether first-line antihypertensive drugs ameliorate the dysbiosis state in hypertension, and to test if this modification contributes to their blood pressure (BP) lowering properties in a genetic model of neurogenic hypertension. Twenty-week-old male Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were untreated or treated with captopril, amlodipine or hydrochlorothiazide. A faecal microbiota transplantation (FMT) experiment was also performed by gavage of faecal content from donor SHR-treated groups to SHR recipients for 3 weeks. Faeces from SHR showed gut dysbiosis, characterized by lower acetate- and higher lactate-producing bacteria and lower strict anaerobic bacteria. All three drugs increased the anaerobic bacteria proportion, captopril and amlodipine restored the proportion of acetate-producing bacterial populations to WKY levels, whereas hydrochlorothiazide decreased butyrate-producing bacteria. Captopril and amlodipine decreased gut pathology and permeability and attenuated sympathetic drive in the gut. Both drugs decreased neuroinflammation and oxidative stress in the hypothalamic paraventricular nuclei. Hydrochlorothiazide was unable to reduce neuroinflammation, gut sympathetic tone and gut integrity. FMT from SHR-amlodipine to SHR decreased BP, ameliorated aortic endothelium-dependent relaxation to acetylcholine, lowered NADPH oxidase activity, aortic Th17 infiltration and reduced neuroinflammation, whereas FMT from SHR-hydrochlorothiazide did not have these effects. First-line antihypertensive drugs induced different modifications of gut integrity and gut dysbiosis in SHR, which result in no contribution of microbiota in the BP lowering effects of hydrochlorothiazide, whereas the vasculo-protective effect induced by amlodipine involves gut microbiota reshaping and gut-immune system communication.

Extraction, purification, structural modification, activities and application of polysaccharides from different parts of mulberry.

The mulberry plant is a member of the Moraceae family and belongs to the Morus genus. Its entire body is a treasure, with mulberries, mulberry leaves, and mulberry branches all suitable for medicinal use. The main active ingredient in mulberries is mulberry polysaccharide. Studies have shown that polysaccharides from different parts of mulberry exhibit antioxidant, antidiabetic, antibacterial, anti-inflammatory, and blood pressure-lowering properties. There are more studies on the biological activities, extraction methods, and structural characterization of polysaccharides from different parts of mulberry. However, the structural characterization of mulberry polysaccharides is mostly confined to the types and proportions of monosaccharides and the molecular weights of polysaccharides, and there are fewer systematic studies on polysaccharides from different parts of mulberry. In order to better understand the bioactive structure of mulberry polysaccharides, this article discusses the recent research progress in the extraction, separation, purification, bioactivity, structural modification, and application of polysaccharides from different parts of mulberry (mulberry leaves, mulberry fruits, and mulberry branches). It also delves into the pharmacological mechanisms of action of mulberry polysaccharides to provide a theoretical basis for further research on mulberry polysaccharides with a view to their deeper application in the fields of feed and nutraceuticals.

Bioactive Peptides from Ruditapes philippinarum Attenuate Hypertension and Cardiorenal Damage in Deoxycorticosterone Acetate-Salt Hypertensive Rats.

Hypertension is a common disease that affects human health and can lead to damage to the heart, kidneys, and other important organs. In this study, we investigated the regulatory effects of bioactive peptides derived from Ruditapes philippinarum (RPP) on hypertension and organ protection in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. We found that RPPs exhibited significant blood pressure-lowering properties. Furthermore, the results showed that RPPs positively influenced vascular remodeling and effectively maintained a balanced water-sodium equilibrium. Meanwhile, RPPs demonstrated anti-inflammatory potential by reducing the serum levels of inflammatory cytokines (TNF-α, IL-2, and IL-6). Moreover, we observed the strong antioxidant activity of RPPs, which played a critical role in reducing oxidative stress and alleviating hypertension-induced damage to the aorta, heart, and kidneys. Additionally, our study explored the regulatory effects of RPPs on the gut microbiota, suggesting a possible correlation between their antihypertensive effects and the modulation of gut microbiota. Our previous studies have demonstrated that RPPs can significantly reduce blood pressure in SHR rats. This suggests that RPPs can significantly improve both essential hypertension and DOAC-salt-induced secondary hypertension and can ameliorate cardiorenal damage caused by hypertension. These findings further support the possibility of RPPs as an active ingredient in functional anti-hypertensive foods.

Antispasmodic, cardioprotective and blood-pressure lowering properties of Gomphrena perennis L. and its mechanisms of action

BackgroundGomphrena perennis L. is a native plant of South America whose pharmacological properties have not been studied yet. AimTo evaluate the cardiovascular and intestinal pharmacological effects of Gomphrena perennis L. leaves tincture (GphT) and the mechanisms involved. Experimental procedureThe chromatographic profile of GphT was done. Its ex vivo effects were evaluated by contractile concentration-response curves (CRCs) obtained from the agonist carbachol or calcium found in isolated rat small intestine, as well as in the relaxant CRCs. Cardiac effects were evaluated on isolated rat hearts exposed to ischemia/reperfusion (I/R). Experiments in vivo were performed to evaluate the diuretic activity in conscious rats and the hypotensive effect in anaesthetised rats. ResultsFifteen flavonoids were identified in GphT by HPLC-UV, including diosmin. GphT induced a non-competitive inhibition in both carbachol and calcium CRCs on rat small intestine. The first was not affected by indomethacin. Moreover, GphT, unlike diosmin, relaxed the contracture produced by a high-potassium solution in a dose-dependently way. Neither propranolol nor l-NAME changed it. GphT did not show diuretic activity but induced hypotension insensitive to l-NAME. While GphT perfusion of isolated hearts increased injury consequent to I/R, oral administration was cardioprotective and reversed by l-NAME. However, diosmin did not improve the post-ischemic recovery. ConclusionsThis study supports the use of Gomphrena perennis L. tincture as an antispasmodic and hypotensive agent. Moreover, it has been demonstrated to be preventive of post-ischemic cardiac dysfunction. However, diosmin would not be responsible for these effects.

Effect of preserved eggs on the health of SD rats, and anti-tumor action of HT-29 cells.

Preserved eggs are traditional alkali-pickled food in China and have been enjoyed by consumers and extensively studied by researchers for their nutritional tastes and their anti-tumor, anti-inflammatory, antioxidant, lipid-lowering, and blood pressure-lowering properties. To study the anti-tumor effects of preserved eggs, this project observed the health on rats, and anti-tumor effects and separated anti-tumor active components on HT-29 cells. SD rats fed for 80 days showed that preserved eggs had no significant effect on weight, food intake, blood pH, liver tissues, or organ indices. Preserved eggs significantly increased blood levels of oxidative stress markers SOD and CAT, decreased MDA levels by 0.46, 0.23, and 0.25 times. Moreover, they also increased the level of IL-2 from 1233 to 1340 pg/mL. Two water-soluble bioactive peptide fractions, B1 and B2, with molecular weights ≥10 kDa were further obtained from preserved eggs by ultrafiltration and Superdex Peptide 10/300 GL. The potential mechanism of B1 and B2 is to activate the internal mitochondrial apoptotic pathway and induce apoptosis by up-regulating the expression of the pro-apoptotic factors cytochrome C, caspase-3, and caspase-9 mRNA in HT-29 cells.

Impact of Lisinopril on Cardiometabolic Risk Factors in Sisters of Women With Polycystic Ovary Syndrome.

Women with polycystic ovary syndrome (PCOS), the most common endocrinopathy in reproductive age, are characterized by increased cardiometabolic risk. Similar hormonal and metabolic changes were found in their siblings. The purpose of our study was to compare blood pressure-lowering and pleiotropic effects of lisinopril between sisters of women with PCOS and their unrelated peers. The study included two age-, body mass index-, and blood pressure-matched groups of women with grade 1 hypertension: 26 sisters of PCOS probands (Group 1) and 26 individuals without a family history of PCOS (Group 2), receiving 10-40 mg of lisinopril daily. Blood pressure, glucose homeostasis markers, plasma levels of lipids (androgens, estradiol, high-sensitivity C-reactive protein (hsCRP), homocysteine, fibrinogen, and uric acid), and urinary albumin-to-creatinine ratio (UACR) were measured before lisinopril treatment and 6 months later. At baseline, the study groups differed in insulin sensitivity, testosterone, free androgen index (FAI), hsCRP, homocysteine, and UACR. Blood pressure-lowering properties of lisinopril did not differ between the groups. The decrease in homocysteine and UACR, although observed in both groups, was stronger in Group 2 than in Group 1. Only in women without a family history of PCOS lisinopril improved insulin sensitivity and reduce hsCRP, fibrinogen, and uric acid. The remaining markers did not change throughout the study. Cardiometabolic effects of lisinopril correlated with testosterone, free androgen index, and changes in insulin sensitivity. The obtained results suggest that cardiometabolic effects of lisinopril may be slightly less pronounced in sisters of women with PCOS than in women without a family history of this disorder.

Molecular Docking and ADME Analysis of L-Phe -L-Tyr Dipeptide

Hypertension is a serious risk factor for various diseases. Therefore, lowering and preventing high blood pressure is a significant issue. Blockage of the renin-angiotensin-aldosterone system (RAAS), which controls blood pressure, is important to reduce blood pressure and consequently reduce symptoms of heart failure. This blockage can be carried out by angiotensin-converting enzyme (ACE) and angiotensin II receptor blockers (ARBs). The phenylalanyltyrosine (H-Phe-Tyr-OH, Phe-Tyr, L-Phe-L-Tyr, L-phenylalanyl-L-tyrosine) dipeptide examined in this study is an important structure that shows blood pressure lowering properties. For this reason, the potential of the peptide to be an ACE inhibitor or ARB was investigated. The molecular activity of the Phe-Tyr dipeptide was compared with antihypertensive drugs using theoretical calculations. Molecular docking method, one of these theoretical methods, has a considerable process in illuminating biochemical processes by investigating the interactions of drugs (ligands) with targeted receptors. In this theoretical study, molecular docking analyses of H-Phe-Tyr-OH dipeptide with ACE and Angiotensin II type 1 receptor (AT1R) were implemented. The interaction types and interaction regions of the peptide were also determined in comparison with drug molecules (Captopril, Enalapril, Telmisartan and Eprosartan) that are ACE inhibitors and ARBs. Lastly, ADME (absorption, distribution, metabolism, and excretion) analysis of the H-Phe-Tyr-OH dipeptide was also performed to estimate its drug potential. In this study, the pharmacokinetic properties of Phe-Tyr dipeptide and its mechanism of action with ACE and AT1R were investigated for the first time by molecular docking and ADME calculations.

Heterogenous improvements in endothelial function by sub-blood pressure lowering doses of ARBs result in major anti-aortic root remodeling effects

Low basal nitric oxide (NO) production is associated with a dysfunctional endothelium and vascular diseases. We have shown that some angiotensin II (AngII) receptor type 1 (AT1R) blockers (ARBs), a group of clinic-approved blood pressure (BP)-lowering medications, are also capable of activating endothelial function acutely and chronically, both ex vivo and in vivo, in pleiotropic, AngII-independent fashions, which suggested that endothelial function enhancement with ARBs may be independent of their well-documented BP lowering properties. Herein, we attempt to identify the most potent ARB at activating endothelial function when administered at sub-BP-lowering doses and determine its anti-aortic root remodeling properties in a model of Marfan syndrome (MFS). Amongst the 8 clinically available ARBs tested, only telmisartan and azilsartan induced significant (70% and 49%, respectively) NO-dependent inhibition of aortic contractility when administered for 4 weeks at sub-BP lowering, EC5 doses. Low-dose telmisartan (0.47 mg/kg) attenuated MFS-associated aortic root widening, medial thickening, and elastic fiber fragmentation to the same degree as high-dose telmisartan (10 mg/kg) despite wide differences in BP lowering between the two doses. Our study suggests that telmisartan is the most potent ARB at promoting increased endothelial function at low sub-BP doses and that it retained major aortic root widening inhibition activities. ARBs may enhance endothelial function independently from BP-lowering pathways, which could lead to new therapeutic approaches.

서로 다른 인공광원 하에서 기내 발아 및 배양된 새싹 황기의 생육 특성및 생리활성 검정

Background: Astragalus membranaceus Bunge is a plant belonging to the Leguminosae family that is used in oriental medicine as a diuretic or a tonic and has blood pressure-lowering properties. Several other propertieds, including reduction of blood sugar, antitumor, and antiviral properties, have also been reported.BRMethods and Results: A. membranaceus treated exposed to blue light showed the maximum value for plant height, root length, and leaf number. Antioxidant activity was also observed under white light. The maximum values of total phenol and total flavonoid content were observed under white light and blue light, respectively. To assess the whitening and anti-wrinkle activities, the tyrosinase inhibiting activity was determined, which showed the highest value at the maximum concentration of 5,000 ㎍/㎖ in blue light-treated A. membranaceus.BRConclusions: The use of LED light will benefit the commercial production of A. membranaceus for cosmetic and food purposes.

Association between Legume Consumption and Risk of Hypertension in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Cohort.

Hypertension is a significant and preventable cardiovascular disease risk factor. Growing evidence suggests legumes have blood-pressure (BP) lowering properties. However, there is little population-based research on legume intake and hypertension risk in Western populations. The objective was to investigate the relationship between legume intake and blood pressure by using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) Norfolk cohort. Further, to identify any potential legume intake that confers benefits in relation to blood pressure. We included participants who completed both 7-day food diaries to assess legume intake and undertook a first (1993–1997) and second (1998–2000) health check from the EPIC-Norfolk prospective study. Legume consumption was categorized using percentile cut off values. We used multivariate logistic regression models to calculate the odds ratio of hypertension (defined as >140 mmHg systolic and/or >90 mmHg diastolic blood pressure) at the second health check, stratified by legume intake, adjusting for antihypertensive medication use and demographic, socioeconomic and lifestyle covariates. A total of 7522 participants were included with mean age (± SD) of 58.0 ± 8.9 years. The follow-up time was 3.7 years (range: 2.1–6.6 years). Mean legume consumption was 17.3 ± 16.3 g/day. Participants in the 97th percentile of legume intake had the lowest odds of subsequent hypertension (OR: 0.71; 95% CI: 0.52, 0.96). Legume consumption between 55–70 g/day was associated with reduced odds of hypertension (OR: 0.57; 95% CI: 0.37, 0.88); sex-specific values for men and women were 0.64 (0.38, 1.03) and 0.32 (0.12, 0.88), respectively. In this UK population, legume intake of 55–70 g/day was associated with a lower subsequent risk of hypertension. Given the low legume intake in the UK and Western countries, dietary guidance to increase intake above 55 g/day may lower the burden of hypertension and associated diseases.

Synthesis and Biological Activity of 1,3,4-Oxadiazoles Used in Medicine and Agriculture

Biologically active compounds play a key role in the fight against diseases affecting both human and animal living organisms, as well as plants. Finding out about new molecules with a potential biological effect, not yet described in the literature, is one of the most important aspects in the development of medicine and agriculture. Compounds showing desirable biological activity include heterocyclic moieties such as 1,3,4-oxadiazoles. The oxadiazole molecule is composed of two nitrogen atoms and one oxygen atom, forming a five-membered heterocyclic ring. Structures of this type have been successfully used in the treatment of various diseases in humans and animals, and play an important role in modern agriculture. It has been proven that many oxadiazole derivatives exhibit antibacterial, antiviral, blood pressure lowering, antifungal, antineoplastic, anticancer, antioxidant, anti-inflammatory and analgesic properties. In addition, compounds based on 1,3,4-oxadiazole can act as plant protection agents due to their herbicidal, insecticidal and fungicidal activity. Due to the constantly growing interest in heterocyclic systems of this nature, new methods of obtaining complex structures containing oxadiazole rings are sought. This article discusses various methods of synthesis of 1,3,4-oxadiazole derivatives exhibiting biological activity. Based on these techniques, these compounds could be used in the future in medicine and agriculture.

Recent findings on the cellular and molecular mechanisms of action of novel food-derived antihypertensive peptides

Hypertension impacts negatively on the quality of life of sufferers, and complications associated with uncontrolled hypertension are life-threatening. Hence, many research efforts are exploring the antihypertensive properties of bioactive peptides derived from food proteins using in vitro ACE-inhibitory assay, experimentally-induced and spontaneous hypertensive rats, normotensive and hypertensive human models. In this study, the cellular and molecular mechanisms of blood pressure-lowering properties of novel peptides reported in recent studies (2015-July 30, 2021) were discussed. In addition to common mechanisms such as the inhibition of angiotensin I-converting enzyme (ACE) and renin activities, recently recognized mechanisms through which bioactive peptides exert their antihypertensive properties including the induction of vasodilation via upregulation of cyclo-oxygenase (COX) and prostaglandin receptor and endothelial nitric oxide synthase expression and L-type Ca2+ channel blockade were presented. Similarly, emerging mechanisms of blood pressure-lowering by bioactive peptides such as modulation of inflammation (TNF-α, and other cytokines signaling), oxidative stress (Keap-1/Nrf2/ARE/HO-1 and related signaling pathways), PPAR-γ/caspase3/MAPK signaling pathways and inhibition of lipid accumulation were discussed. The review also highlighted factors that influence the antihypertensive properties of peptides such as method of hydrolysis (type and number of enzymes, and chemical used for hydrolysis, and microbial fermentation), and amino acid sequence and chain length of peptides.

First-in-Human Study of MANP: A Novel ANP (Atrial Natriuretic Peptide) Analog in Human Hypertension.

[Figure: see text].

Presence of antioxidants and nitric-oxide precursors in Mimosa pudica extract

Blood pressure lowering effect of Mimosa pudica induced by dieresis was reported earlier. As a diuretic it enhances urine outflow, decreases plasma volume, venous return; and thereby, reduce blood pressure. Besides the diuretic agent, some other blood pressure lowering substance may also be present in Mimosa pudica. Present study was undertaken to reveal the presence of antioxidants and nitrite in Mimosa pudica extract, which may help to reduce blood pressure. Methanolic extract of Mimosa pudica (using 80% methanol) was lyophilised to obtain dried Mimosa pudica Extract (MPE). For Total phenolic content estimation Folin’s method and for estimation of flavonoids, Aluminium chloride method were followed. The radical scavenging and superoxide anion radical scavenging activity were measured following standardised methods. Nitrite content of MPE at different dilutions (10-100 µl in methanol) was measured following standardised procedure keeping sodium nitrite as the standard. Present study noted presence of favonoids and phenolic compounds and also noted antioxidant property in the aforesaid extract that exhibited DPPH+ and superoxide scavenging activities. Besides that, this study also revealed formation of nitrites in the extract of Mimosa pudica in a dose dependent manner. Nitrite is the precursor of nitric oxide (NO). NO is a potent vasodilator that decreases blood pressure. Present study indicated the presence of both antioxidants and nitrites in Mimosa pudica extract; both of which have blood pressure lowering properties indicating it as a blood pressure lowering agent; and helpful in the maintenance of vascular health.

Sex Differences in Blood Pressure Variability in response to Sodium and Potassium Diets

It is well established that Americans consume more salt than recommended by the Dietary Guidelines for Americans. High sodium diets have been shown to increase blood pressure (BP) while dietary potassium is known for its BP lowering properties. Elevated BP variability (BPV), as indicated by spontaneous fluctuations in BP, is associated with cardiovascular morbidity and mortality. Although no recommendations exist for targeting elevated BPV, understanding how different dietary components affect BPV could be important to reduce CVD. Limited literature from rodent and human studies suggests a relation between a high sodium diet and an increased BPV. Additionally, mechanisms regulating BP between men and women differ which may lead to the hypothesis that BPV differs as well. Thus, the interactive effects of dietary sodium and potassium on BPV in humans are unknown as well as whether potential sex differences exist. The purpose of this study was to compare BP and BPV responses to varying dietary levels of sodium and potassium in salt-resistant, healthy, normotensive young adults. Twenty women (27±1 yrs. old; SBP: 112±3 mmHg; DBP: 71±1 mmHg; BMI: 24.1±0.7 kg/m2) and 17 men (26±1 yrs. old; SBP: 117±3 mmHg; DBP: 75±2 mmHg; BMI: 24.4±0.7 kg/m2) completed 7 days each of the following diets: moderate potassium/low sodium diet (65 mmol potassium/50 mmol sodium; MK/LS), a moderate potassium/high sodium diet (65 mmol potassium/300 mmol sodium; MK/HS) and a high potassium/high sodium (120 mmol potassium/300 mmol sodium; HK/HS) in random order. BP and BPV were calculated from 24 h ambulatory BP monitoring on day 6 of each diet. Average Real Variability (ARV) was used as an index of BPV. A mixed-model ANOVA was performed with a Tukey post hoc test with diet as a within subject factor and sex as a between subject factor to determine whether differences existed between men and women on each diet. For 24 h SBP, the main effect of sex was significant (p=0.01) and the sex*diet interaction was significant (p=0.03) such that men had a higher 24 h SBP than women on the HK/HS diet (117±2 mmHg vs 112±1 mmHg, p=0.02). On the MK/LS and MK/HS diets, 24 h SBP was not different between men and women (p>0.05). For 24 h DBP, the main effect of diet was significant (p=0.009) such that 24 h DBP was higher on the MK/LS diet vs HK/HS diet (69±1 mmHg vs 67±1 mmHg, p=0.01) and higher on MK/LS diet compared to MK/HS diet regardless of sex (69±1 mmHg vs 68±1 mm Hg, p=0.02). For 24 h SBP ARV, the main effects of diet and sex and the interaction of sex*diet were not significant (all p>0.05). For 24 h DBP ARV, the main effect of sex was significant (p=0.006) such that men had higher variability regardless of diet (9±0.2 mmHg vs 7±0.2 mm Hg). Our results suggest that in the context of a high sodium diet, potassium may help lower BP in women but not in men. In addition, men tended to have a higher BPV compared to women regardless of the diet. Future studies are warranted to further study the differential response of men and women to the effectiveness of dietary interventions for reducing CVD risk.

Medical management of resistant hypertension: the role of sodium-glucose cotransporter 2 inhibitors (SGLT2i).

Controlling hypertension to the desired target is commonly unsuccessful and requires multi-drug regimen, which can lead to undesirable side effects. Resistant hypertension (RH) is more cumbersome to deal with and has robust morbidity and mortality burden even with current multiple medical options. Herein, we review the literature for the potential role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as a treatment option for hypertension and RH. With more recent randomized controlled trials (RCTs), SGLT2i have gained more recognition for their renal and cardiovascular protection as well as mortality benefit that are believed to be medication class-related effects. Multiple RCTs have evaluated blood pressure (BP) lowering properties of SGLT2i, as a primary or secondary end point, in diabetic and nondiabetic patients, yet trials are scarce in studying SGLT2i as first-line antihypertensives, or as add-on agents for treating RH. Finding the right medical therapy in treating hypertension, especially RH, is commonly onerous when it comes to achieving BP targets, avoiding medication side effects, and aiming for the best outcomes. Utilizing existing drugs like SGLT2i or exploring other novel agents with more RCTs for these purposes will be beneficial. The addition of SGLT2i to the therapeutic armamentarium in patients with RH should be considered as a target for upcoming RCTs.

Addition of Citrus Leaf Extract into Frying Oil Prevents Hypertension and Improves Vascular Reactivity in Heated Oil-Fed Rats

The use of repeatedly heated frying oil is hazardous to health, due to oxidative process that occurs in the oil. Addition of an additive with antioxidant property could lessen the detrimental effects of repeated frying in the oils. Citrus leaf extract (CLE) supplementation was reported to possess antioxidant and blood pressure-lowering properties. Our study aimed to determine the effects of CLE addition into frying oil in rats fed with repeatedly heated oil diet. Seven groups of male Sprague-Dawley rats were given fresh and heated oil diets (five-time- and ten-time-heated palm oil), with and without the CLE addition for 16 weeks. CLE addition decreased peroxide value and augmented the total phenolics content in the heated oils. CLE addition reversed the negative effects of heated oil on nitric oxide level, systolic blood pressure, and vascular reactivity. In conclusion, these findings show that CLE has the ability to reduce oxidative damage caused by thermal degradation in frying oil and subsequently lowers the risk of hypertension in rats that consumed heated oil.