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Fulltext Safety and Efficacy of Dietary Epigallocatechin Gallate Supplementation in Attenuating Hypertension via Its Modulatory Activities on the Intrarenal Renin-Angiotensin System in Spontaneously Hypertensive Rats

Parn KW, Ling WC, Chin JH, Lee SK

Nutrients, 2022 Nov 01;14(21).
PMID: 36364864 DOI: 10.3390/nu14214605

This study aimed to identify the no-observed-adverse-effect level (NOAEL) of dietary epigallocatechin gallate (EGCG) supplementation and its possible antihypertensive and nutrigenomics effects in modulating intrarenal renin-angiotensin system (RAS) gene expression in spontaneously hypertensive rats (SHR). EGCG (50, 250, 500 or 1000 mg/kg b.w. i.g., once daily) was administered to SHR for 28 days. All the SHR survived with no signs of systemic toxicity. Increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and thiobarbituric acid reactive substances (TBARS) were evident in SHR supplemented with 500 and 1000 mg/kg b.w. but not in those supplemented with lower doses of EGCG. Subsequently, the NOAEL of EGCG was established at 250 mg/kg b.w., and the same protocol was replicated to assess its effects on blood pressure and renal RAS-related genes in SHR. The systolic blood pressure (SBP) of the EGCG group was consistently lower than the control group. The mRNA levels of cortical Agtr2 and Ace2 and medullary Agtr2, Ace and Mas1 were upregulated while medullary Ren was downregulated in EGCG group. Statistical analysis showed that SBP reduction was associated with the changes in medullary Agtr2, Ace, and Ren. Dietary EGCG supplementation exhibits antihypertensive and nutrigenomics effects through activation of intrarenal Ace and Agtr2 and suppression of Ren mediators, while a high dose of EGCG induced liver damage in SHR. In future clinical studies, liver damage biomarkers should be closely monitored to further establish the safety of the long-term use of EGCG.

Matched MeSH terms: Antihypertensive Agents/pharmacology
Fulltext Safety and Efficacy of Losartan 50 mg in Reducing Blood Pressure among Patients with Post-Dialysis Euvolemic Hypertension: A Randomized Control Trial

Aftab RA, Khan AH, Adnan AS, Sulaiman SAS, Khan TM

Sci Rep, 2017 12 18;7(1):17741.
PMID: 29255272 DOI: 10.1038/s41598-017-17437-4

The aim of current study was to assess the effectiveness of losartan 50 mg in reducing blood pressure among post-dialysis euvolemic hypertensive patients, observing their survival trends and adverse events during the course of study. A multicentre, prospective, randomised, single-blind trial was conducted to assess the effect of losartan 50 mg every other day (EOD), once a morning (OM) among post-dialysis euvolemic hypertensive patients. Post-dialysis euvolemic assessment was done by a body composition monitor (BCM). Covariate Adaptive Randomization was used for allocation of participants to the standard or intervention arm. Of the total 229 patients, 96 (41.9%) were identified as post-dialysis euvolemic hypertensive. Final samples of 88 (40.1%) patients were randomized into standard and intervention arms. After follow-up of 12 months' pre-dialysis systolic (p

Matched MeSH terms: Antihypertensive Agents/pharmacology
Synthesis and evaluation of chalcone analogues based pyrimidines as angiotensin converting enzyme inhibitors

Bukhari SN, Butt AM, Amjad MW, Ahmad W, Shah VH, Trivedi AR

Pak J Biol Sci, 2013 Nov 01;16(21):1368-72.
PMID: 24511749

Hypertension is a widespread and frequently progressive ailment that imparts a foremost threat for cardiovascular and renal disorders. Mammoth efforts are needed for the synthesis of innovative antihypertensive agents to combat this lethal disease. Chalcones have shown antihypertensive activity through inhibition of Angiotensin Converting Enzyme (ACE). Hence, a series of chalcone analogues is synthesized and used as precursor for the synthesis of novel series of pyrimidines. Precursor chalcones were prepared by reacting aldehydes and ketones in presence of sodium hydroxide followed by synthesis of corresponding pyrimidines by reaction with urea in presence of potassium hydroxide. Both groups were then evaluated for their effects on ACE. The results depicted that pyrimidines were more active than chalcones with methoxy (C5 and P5) substitution showing best results to inhibit ACE. Given that chalcone analogues and pyrimidines show a potential as the angiotensin converting enzyme inhibitors.

Matched MeSH terms: Antihypertensive Agents/pharmacology
Systematic Review and Meta-Analysis for Sexual Dysfunction in Women With Hypertension

Choy CL, Sidi H, Koon CS, Ming OS, Mohamed IN, Guan NC, et al.

J Sex Med, 2019 Jul;16(7):1029-1048.
PMID: 31113742 DOI: 10.1016/j.jsxm.2019.04.007

INTRODUCTION: Sexual dysfunction in hypertensive women is an often-neglected subject despite a reported prevalence of 42.1%. Although few reviews exist, a definitive relationship between hypertension and sexual dysfunction in women has not been clearly established.
AIM: To review the existing literature to definitively examine sexual dysfunction in women with hypertension, in both treated and untreated subjects.
METHODS: We performed a systematic search for published literature of 3 electronic databases (Scopus, EBSCOhost Medline Complete, and Cochrane Library) in August 2018. The search terms with relevant truncation and Boolean were developed according to a population exposure-comparator-outcome model combining pilot searches. The quality of included studies was assessed with the McMaster Critical Review Form for Quantitative Studies. Initial search, limited to the English language, included a total of 2,198 studies. 31 studies (18,260 subjects) met our inclusion criteria and were included in the review. Sexual dysfunction in these studies was measured using different tools. We extracted information of study setting, country, number of subjects, participants' age and blood pressure, comparators, and outcome. We ran a meta-analysis on the presence of sexual dysfunction as an outcome from the following comparisons: (i) hypertensive vs normotensive (ii) treated vs untreated hypertension, and (iii) exposure vs absence of specific class of anti-hypertensive drug.
MAIN OUTCOME MEASURES: Women with sexual dysfunction and hypertension were included.
RESULTS: We found significant sexual dysfunction in women with hypertension compared with the normotensive group (pooled odds ratio [OR] = 2.789, 95% CI = 1.452-5.357, P = .002). However, there was no statistical difference of sexual dysfunction in women with treated or untreated hypertension (OR = 1.229, 95% CI = 0.675-2.236, P = .5). Treatment with alpha-/beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, and diuretics resulted in no statistical difference in sexual dysfunction in hypertensive women.
CLINICAL IMPLICATIONS: Because sexual dysfunction is prevalent in women with hypertension, it is imperative to address the underlying medical condition to manage this important clinical problem.
STRENGTH & LIMITATIONS: Many studies had to be excluded from the meta-analysis, due to unavailability and incompleteness of data. Nevertheless, results of the review are useful to derive recommendations for alerting physicians of the need to routinely assess the sexual functioning of women with hypertension.
CONCLUSION: We conclude that women with hypertension are at increased risk for sexual dysfunction, and our findings imply that evaluation for sexual dysfunction needs to be part of the clinical management guidelines for women with hypertension. Choy CL, Sidi H, Koon CS, et al. Systematic Review and Meta-Analysis for Sexual Dysfunction in Women With Hypertension. J Sex Med 2019;16:1029-1048.

Matched MeSH terms: Antihypertensive Agents/pharmacology*
Fulltext Telemedicine in the management of hypertension: Evolving technological platforms for blood pressure telemonitoring

Wang JG, Li Y, Chia YC, Cheng HM, Minh HV, Siddique S, et al.

J Clin Hypertens (Greenwich), 2021 03;23(3):435-439.
PMID: 33484617 DOI: 10.1111/jch.14194

The prevalence of hypertension is high and still increasing in almost all communities regardless of high, middle, or low income. The control rate remains low in most countries. Telemedicine offers possibilities to improve blood pressure control. The past two decades witnessed the fast evolving telecommunication from telephone transmission to smart mobile phone technology for telemedicine. There is some evidence from randomized controlled trials that telemonitoring improves blood pressure control. However, it requires co-interventions. The emerging new technology may offer even more possibilities in telemonitoring and co-interventions, for instance, an interactive platform between patients and health professionals for the management of hypertension. Telemedicine might ultimately change the situation of the unsatisfactory management of hypertension in many communities. It helps fully utilize antihypertensive treatment, the most effective cardiovascular prevention, to achieve the goal of ending atherosclerosis and arteriosclerosis in humans.

Matched MeSH terms: Antihypertensive Agents/pharmacology
Fulltext The effects of Cicletanine, a new antihypertensive agent on insulin release in rat isolated pancreas by the perfusion technique

Mashori GR, Tariq AR, Shahimi MM, Suhaimi H

Singapore Med J, 1996 Jun;37(3):278-81.
PMID: 8942229

Treatment of hypertension has reduced the incidence of stroke, heart failure and renal failure. However, the incidence of coronary heart disease is not reduced to the same degree. Many of the drugs advocated as first-line drugs in the step-wise therapy have been shown to cause carbohydrate intolerance and it is an independent risk factor in the development of coronary heart disease. It is thus important to identify the antihypertensive drugs that may cause deterioration in glucose tolerance. Cicletanine, the first derivative of the furopyridines, is a new class of antihypertensive agents. It acts directly on vascular endothelium cells by increasing prostacyclin synthesis. It also decreases intracytosolic calcium levels in smooth muscles. The purpose of this study is to evaluate the effects of Cicletanine on insulin release in rat isolated pancreas by the perfusion technique adapted from Loubatieres and co-workers (1972). Doses used were based on therapeutic peak plasma concentration. Diazoxide was used as a positive control ie a known insulin suppressant. Cicletanine at 1/10 and equivalent therapeutic concentrations (0.5 microgram/mL and 5.0 micrograms/mL) did not suppress insulin release. However, at concentration exceeding 10X its therapeutic levels (50 micrograms/mL) it begins to suppress insulin release. In conclusion, Cicletanine did not inhibit insulin release at concentrations within the therapeutic range.

Matched MeSH terms: Antihypertensive Agents/pharmacology*
The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review)

Siti HN, Kamisah Y, Kamsiah J

Vascul. Pharmacol., 2015 Aug;71:40-56.
PMID: 25869516 DOI: 10.1016/j.vph.2015.03.005

The concept of mild chronic vascular inflammation as part of the pathophysiology of cardiovascular disease, most importantly hypertension and atherosclerosis, has been well accepted. Indeed there are links between vascular inflammation, endothelial dysfunction and oxidative stress. However, there are still gaps in our understanding regarding this matter that might be the cause behind disappointing results of antioxidant therapy for cardiovascular risk factors in large-scale long-term randomised controlled trials. Apart from the limitations of our knowledge, limitations in methodology and assessment of the body's endogenous and exogenous oxidant-antioxidant status are a serious handicap. The pleiotropic effects of antioxidant and anti-inflammation that are shown by some well-established antihypertensive agents and statins partly support the idea of using antioxidants in vascular diseases as still relevant. This review aims to provide an overview of the links between oxidative stress, vascular inflammation, endothelial dysfunction and cardiovascular risk factors, importantly focusing on blood pressure regulation and atherosclerosis. In view of the potential benefits of antioxidants, this review will also examine the proposed role of vitamin C, vitamin E and polyphenols in cardiovascular diseases as well as the success or failure of antioxidant therapy for cardiovascular diseases in clinical trials.

Matched MeSH terms: Antihypertensive Agents/pharmacology
Fulltext The use of Piper sarmentosum leaves aqueous extract (Kadukmy™) as antihypertensive agent in spontaneous hypertensive rats

Mohd Zainudin M, Zakaria Z, Megat Mohd Nordin NA

BMC Complement Altern Med, 2015 Mar 10;15:54.
PMID: 25887182 DOI: 10.1186/s12906-015-0565-z

BACKGROUND: The National Health and Morbidity Survey in 2011 estimated that 35.1% (5.7 million) of Malaysian adults aged 18 and older suffer from hypertension. Hypertension is still treated by conventional medicine despite its exact aetiology being unknown. Studies showed that oxidative stress and low availability of nitric oxide (NO) causes an increase in vascular wall tension and increase blood pressure. Piper sarmentosum (PS) a traditional Malay herbal plant is well known for its high antioxidant content. Antioxidant is useful in improving cardiovascular diseases particularly hypertension. Thus, it is beneficial to determine the effect of PS leaves aqueous extract (Kadukmy™) on the blood pressure, NO level, oxidative stress markers and serum cholesterol level of the Spontaneous Hypertensive Rats (SHR).
METHODS: Rats were devided into five groups consisting of three treatment groups and two control groups. Baseline blood investigations were done before and following commencement of treatment. Spontaneous hypertensive rats were treated for 28 consecutive days and the blood pressure was measured weekly.
RESULTS: Kadukmy™ administration showed a significant reduction in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) (P

Matched MeSH terms: Antihypertensive Agents/pharmacology
Toxicity study and blood pressure-lowering efficacy of whey protein concentrate hydrolysate in rat models, plus peptide characterization

Hussein FA, Chay SY, Ghanisma SBM, Zarei M, Auwal SM, Hamid AA, et al.

J Dairy Sci, 2020 Mar;103(3):2053-2064.
PMID: 31882211 DOI: 10.3168/jds.2019-17462

We evaluated the acute (single-dose) and subacute (repeated-dose) oral toxicity of alcalase-hydrolyzed whey protein concentrate. Our acute study revealed no death or treatment-related complications, and the median lethal dose of whey protein concentrate hydrolysate was >2,500 mg/kg. In the subacute study, when the hydrolysate was fed at 3 different concentrations (200, 400, and 800 mg/kg), no groups showed toxicity changes compared with controls. Then, whey protein concentrate hydrolysate was orally administered to spontaneously hypertensive rats. Results revealed significant reductions in blood pressure in a dose-dependent manner, and dosing at 400 mg/kg led to significant blood pressure reduction (-47.8 mm Hg) compared with controls (blood pressure maintained) and the findings of previous work (-21 mm Hg). Eight peptides-RHPEYAVSVLLR, GGAPPAGRL, GPPLPRL, ELKPTPEGDL, VLSELPEP, DAQSAPLRVY, RDMPIQAF, and LEQVLPRD-were sequentially identified and characterized. Of the peptides, VLSELPEP and LEQVLPRD showed the most prominent in vitro angiotensin-I converting enzyme inhibition with half-maximal inhibitory concentrations of 0.049 and 0.043 mM, respectively. These findings establish strong evidence for the in vitro and in vivo potential of whey protein concentrate hydrolysate to act as a safe, natural functional food ingredient that exerts antihypertensive activity.

Matched MeSH terms: Antihypertensive Agents/pharmacology*
Vasodilation and Antihypertensive Activities of Swietenia macrophylla (Mahogany) Seed Extract

Ch'ng YS, Loh YC, Tan CS, Ahmad M, Asmawi MZ, Wan Omar WM, et al.

J Med Food, 2018 Mar;21(3):289-301.
PMID: 29420109 DOI: 10.1089/jmf.2017.4008

The seeds of Swietenia macrophylla King (SM) (Meliaceae) are used as a folk medicine for the treatment of hypertension in Malaysia. However, the antihypertensive and vasorelaxant effects of SM seeds are still not widely studied. Thus, this study was designed to investigate the in vivo antihypertensive effects and in vitro mechanism of vasorelaxation of a 50% ethanolic SM seed extract (SM50) and the fingerprint of SM50 was developed through tri-step Fourier transform infrared (FTIR) spectroscopy. The vasorelaxant activity and the underlying mechanisms of SM50 were evaluated on thoracic aortic rings isolated from Sprague-Dawley rats in the presence of antagonists. The pharmacological effect of SM50 was investigated by oral administration of spontaneously hypertensive rats (SHRs) with three different doses of SM50 (1000, 500, and 250 mg/kg/day) for 4 weeks and their systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were measured weekly using tail-cuff method. The tri-step FTIR macro-fingerprint of SM50 showed that SM50 contains stachyose, flavonoids, limonoids, and ester, which may contribute to its vasorelaxant effect. The results showed that the vasorelaxant activity of SM50 was mostly attributed to channel-linked receptors pathways through the blockage of voltage-operated calcium channels (VOCC). SM50 also acts as both potassium channels opener and inositol triphosphate receptor (IP3R) inhibitor, followed by β2-adrenergic pathway, and ultimately mediated through the nitric oxide/soluble guanylyl cyclase/cyclic 3',5'-guanosine monophosphate (NO/sGC/cGMP) signaling pathways. The treatment of SM50 also significantly decreased the SBP and DBP in SHRs. In conclusion, the antihypertensive mechanism of SM50 was mediated by VOCC, K+ channels, IP3R, G-protein-coupled β2-adrenergic receptor, and followed by NO/sGC/cGMP signaling mechanism pathways in descending order. The data suggested that SM50 has the potential to be used as a herbal medicament to treat hypertension.

Matched MeSH terms: Antihypertensive Agents/pharmacology
Fulltext What is new in the 2018 Chinese hypertension guideline and the implication for the management of hypertension in Asia?

Wang JG, Chia YC, Chen CH, Park S, Hoshide S, Tomitani N, et al.

J Clin Hypertens (Greenwich), 2020 03;22(3):363-368.
PMID: 31955513 DOI: 10.1111/jch.13803

The new Chinese hypertension guideline comprehensively covers almost all major aspects in the management of hypertension. In this new guideline, hypertension remains defined as a systolic/diastolic blood pressure of at least 140/90 mm Hg. For risk assessment, a qualitative approach is used similarly as in previous Chinese guidelines according to the blood pressure level and the presence or absence of other risk factors, target organ damage, cardiovascular complications, and comorbid diseases. The therapeutic target is 140/90 mm Hg in general, and if tolerated, especially in high-risk patients, can be more stringent, that is, 130/80 mm Hg. However, a less stringent target, that is, 150/90 mm Hg, is used in the younger (65-79 years, if tolerated, 140/90 mm Hg) and older elderly (≥80 years). Five classes of antihypertensive drugs, including β-blockers, can be used either in initial monotherapy or combination. The guideline also provided information on the management of hypertension in several special groups of patients and in the presence of secondary causes of hypertension. To implement the guideline recommendations, several nationwide hypertension control initiatives are being undertaken with new technology. The new technological platforms hopefully will help improve the management of hypertension and generate scientific evidence for future hypertension guidelines, including a possible Asian hypertension guideline in the near future.

Matched MeSH terms: Antihypertensive Agents/pharmacology*

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