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  1. Prevalence of true resistant hypertension in those referred for uncontrolled hypertension in Malaysia: A comparison using different definitions
    Yeo JJP, Yeo LS, Tan SSN, Delailah DDRA, Lee SWH, Hu ATH, et al.
    Hypertens Res, 2024 Feb;47(2):352-357.
    PMID: 37673957 DOI: 10.1038/s41440-023-01418-4
    Resistant hypertension is a well-recognised clinical challenge. However, the definition and epidemiology of true resistant hypertension (RH) are less understood, especially in Asia. This cross-sectional study examined the prevalence of RH referred from primary care clinics based on various guidelines. RH was defined as blood pressure (BP) being above the threshold using ambulatory blood pressure monitoring despite adequate lifestyle measures and optimal treatment with ≥3 medications at maximally tolerated doses. Between one in four (n = 94, 24.0% using Malaysian guidelines) and up to two-thirds (n = 249, 63.7% using 2018 American guidelines) of adults referred for uncontrolled hypertension met the criteria of true RH. Of those with RH, a further one-quarter (n = 26, 26.6%) were deemed to have refractory hypertension (elevated BP despite treatment with at least 5 antihypertensive medications). Adults with RH were generally younger, more likely to be male, had a higher BMI and were more likely to have gout, CKD, and angina compared to those with controlled hypertension. The prevalence of RH amongst Asian adults with poor hypertension control is high. A concerted effort is needed to reduce the high burden of RH, especially among this population.
    Matched MeSH terms: Antihypertensive Agents/pharmacology
  2. 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
  3. Fulltext Epigallocatechin gallate (EGCG) alleviates vascular dysfunction in angiotensin II-infused hypertensive mice by modulating oxidative stress and eNOS
    Mohd Sabri NA, Lee SK, Murugan DD, Ling WC
    Sci Rep, 2022 Oct 21;12(1):17633.
    PMID: 36271015 DOI: 10.1038/s41598-022-21107-5
    Epigallocatechin gallate (EGCG) has been shown to have antihypertensive activity. However, the role of epigallocatechin gallate (EGCG) in improving vascular function via modulation of endothelial nitric oxide synthase (eNOS) in hypertensive subjects is not well researched. Angiotensin II-infused hypertensive mice (8-10 weeks old) received EGCG (50 mg/kg/day) for 14 days via oral gavage. The arterial systolic blood pressure (SBP) was measured using the tail-cuff method every three days. At the end of the treatment, the vascular reactivity of the isolated aortae was studied using wire myographs. The level of nitric oxide (NO), cyclic guanosine monophosphate (cGMP) and tetrahydrobiopterine (BH4) were determined using assay kits while the presence of proteins (NOS, p-eNOS and NOx-2) were determined using by Western blotting. In vivo treatment with EGCG for 14 days significantly attenuated the increase in SBP, alleviated the vascular dysfunction, increased the vascular cGMP and BH4 level as well as the expression of p-eNOS and decreased elevated ROS level and NOx-2 protein in angiotensin II-infused hypertensive mice. Collectively, treatment with EGCG in hypertensive mice exerts a blood pressure lowering effect which is partly attributed to the improvement in the vascular function due to its ability to reduce vascular oxidative stress in the aortic tissue leading to a decrease in eNOS uncoupling thus increasing NO bioavailability.
    Matched MeSH terms: Antihypertensive Agents/pharmacology
  4. Fulltext Mental distress along the cascade of care in managing hypertension
    Ang CW, Tan MM, Bärnighausen T, Reininghaus U, Reidpath D, Su TT
    Sci Rep, 2022 Sep 23;12(1):15910.
    PMID: 36151113 DOI: 10.1038/s41598-022-20020-1
    Hypertension might be a contributing factor of mental illness. The aim of this study was to investigate the association between different levels of hypertension care and mental distress among hypertensive individuals in Malaysia. We constructed a hypertension care cascade using data of 6531 hypertensive individuals aged ≥ 35 years that were collected as part of the community health survey conducted in 2013 in the South East Asia Community Observatory. We examined the association between the status of hypertension care and mental distress using multiple logistic regressions. Respondents who had not been screened for hypertension and those who had uncontrolled blood pressure (BP) had higher odds of depression, anxiety and, stress compared to those who had been screened and those who had controlled BP, respectively. Respondents who were not taking antihypertensive medication had lower odds of depression and anxiety compared to those who were on medication. There was an association between different levels of hypertension care and mental distress. The application of a hypertension care cascade may help improve the provision of mental health support in primary care clinics. Specific mental health interventions could be provided for patients with particular needs along the cascade.
    Matched MeSH terms: Antihypertensive Agents/pharmacology
  5. Fulltext Role of α1-blockers in the current management of hypertension
    Li H, Xu TY, Li Y, Chia YC, Buranakitjaroen P, Cheng HM, et al.
    J Clin Hypertens (Greenwich), 2022 Sep;24(9):1180-1186.
    PMID: 36196467 DOI: 10.1111/jch.14556
    There is emerging evidence that α1-blockers can be safely used in the treatment of hypertension. These drugs can be used in almost all hypertensive patients for blood pressure control. However, there are several special indications. Benign prostatic hyperplasia is a compelling indication of α1-blockers, because of the dual treatment effect on both high blood pressure and lower urinary tract symptoms. Many patients with resistant hypertension would require α1-blockers as add-on therapy. Primary aldosteronism screen is a rapidly increasing clinical demand in the management of hypertension, where α1-blockers are useful for blood pressure control in the preparation for the measurement of plasma aldosterone and renin. Nonetheless, α1-blockers have to be used under several considerations. Among the currently available agents, only long-acting α1-blockers, such as doxazosin gastrointestinal therapeutic system 4-8 mg daily and terazosin 2-4 mg daily, should be chosen. Orthostatic hypotension is a concern with the use of α1-blockers especially in the elderly, and requires careful initial bedtime dosing and avoiding overdosing. Fluid retention is potentially also a concern, which may be overcome by combining an α1-blocker with a diuretic.
    Matched MeSH terms: Antihypertensive Agents/pharmacology
  6. Blood pressure and urine metabolite changes in spontaneously hypertensive rats treated with leaf extract of Ficus deltoidea var angustifolia
    Kamal MSA, Mediani A, Kasim N, Ismail NH, Satar NA, Azis NA, et al.
    J Pharm Biomed Anal, 2022 Feb 20;210:114579.
    PMID: 35016031 DOI: 10.1016/j.jpba.2021.114579
    Ficus deltoidea var angustifolia (FD-A) reduces blood pressure in spontaneously hypertensive rats (SHR) but the mechanism remains unknown. Changes in urine metabolites following FD-A treatment in SHR were, therefore, examined to identify the mechanism of its antihypertensive action. Male SHR were given either FD-A (1000 mg kg-1 day-1) or losartan (10 mg kg-1 day-1) or 0.5 mL of ethanolic-water (control) daily for 4 weeks. Systolic blood pressure (SBP) was measured every week and urine spectra data acquisition, on urine collected after four weeks of treatment, were compared using multivariate data analysis. SBP in FD-A and losartan treated rats was significantly lower than that in the controls after four weeks of treatment. Urine spectra analysis revealed 24 potential biomarkers with variable importance projections (VIP) above 0.5. These included creatine, hippurate, benzoate, trimethylamine N-oxide, taurine, dimethylamine, homocysteine, allantoin, methylamine, n-phenylacetylglycine, guanidinoacetate, creatinine, lactate, glucarate, kynurenine, ethanolamine, betaine, 3-hydroxybutyrate, glycine, lysine, glutamine, 2-hydroxyphenylacetate, 3-indoxylsulfate and sarcosine. From the profile of these metabolites, it seems that FD-A affects urinary levels of metabolites like taurine, hypotaurine, glycine, serine, threonine, alanine, aspartate and glutamine. Alterations in these and the pathways involved in their metabolism might underlie the molecular mechanism of its antihypertensive action.
    Matched MeSH terms: Antihypertensive Agents/pharmacology
  7. Discovery of trans-3,4,4'-trihydroxystilbene as new lead vasorelaxant agent for antihypertensive drug development
    Loh YC, Chan SY, Oo CW, Yam MF
    Life Sci, 2021 Aug 01;278:119560.
    PMID: 33915131 DOI: 10.1016/j.lfs.2021.119560
    AIMS: The structure-vasorelaxant activity relationships (SARs) assessment in previous study has found that trans-3,4,4'-trihydroxystilbene (344OH) could potentially act as a vasorelaxing agent with demonstration of over 2-fold maximal relaxation (Rmax) compared to its analogue, resveratrol. The present study focuses on the mechanism of actions and pathways employed by 344OH and compared to its analogue to further speculate the SAR of stilbenoids towards vasorelaxation.

    MATERIALS AND METHODS: The 344OH employed in present study was synthesized based on the protocol in previous study. The vascular responses towards the cumulative addition of 344OH were evaluated using in vitro rat aortic rings assays.

    KEY FINDINGS: The pEC50 and Rmax values were found to be 4.33 ± 0.05 and 106 ± 3.99%, respectively. Results showed that the vasorelaxation of 344OH were predominated by G-protein-coupled muscarinic- (M3) and β2-adrenergic receptors, followed by PGI2/AC/cAMP- and NO/sGC/cGMP-dependent pathways. It was also identified that 344OH employed voltage-activated- (Kv), calcium-activated- (Kca) and inwardly-rectifying (Kir) potassium channels and act as an antagonist for both VOCC and IP3R while regulating the action potential in the vasculature.

    SIGNIFICANCE: The different position of hydroxyl substituent located in A-ring of the stilbenoid backbone in 344OH compared to resveratrol resulted in a significant difference in mechanistic actions that lead to 344OH's fast-acting and less time-dependent vasorelaxation behaviour. This has substantially increased the potential of 344OH to be developed as an effective antihypertensive drug in future. Present findings further strengthen our inferences where the SARs study approach should be carried out as the mainstream methodology in future drug development research.

    Matched MeSH terms: Antihypertensive Agents/pharmacology*
  8. Fulltext Herbicidal properties of antihypertensive drugs: calcium channel blockers
    Abdullah HSTSH, Chia PW, Omar D, Chuah TS
    Sci Rep, 2021 07 09;11(1):14227.
    PMID: 34244589 DOI: 10.1038/s41598-021-93662-2
    Herbicide resistance is a worldwide problem in weed control. This prompts researchers to look for new modes of action to slow down the evolution of herbicide-resistant weeds. This research aims to determine the herbicidal action of thiazolo[3,2-a]pyrimidines derivatives, which are well known as antihypertensive drugs. The phytotoxic effects of ten compounds were investigated using leaf disc discoloration test and seed germination bioassay. At concentrations of 125 to 250 mg/L, the 5-(3-Fluoro-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester (c) was highly active against Oldenlandia verticillata and Eleusine indica. At application rates of 1.25 to 2.5 kg ai/ha, formulated c demonstrated selective post-emergence and pre-emergence herbicidal activity against O. verticillata, E. indica and Cyperus iria. In the crop tolerance test, formulated c outperformed the commercial herbicide diuron, with aerobic Oryza sativa being the most tolerant, followed by Zea mays, and Brassica rapa. The addition of calcium chloride partially nullified compound c's inhibitory effects on weed shoot growth, indicating that it has potential as a calcium channel blocker. Compound c acted by triggering electrolyte leakage without affecting photosystem II. These findings imply that c could be explored further as a template for developing new herbicides with novel modes of action.
    Matched MeSH terms: Antihypertensive Agents/pharmacology*
  9. Metabolites of the ellagitannin, geraniin inhibit human ACE; in vitro and in silico evidence
    Looi D, Goh BH, Khan SU, Ahemad N, Palanisamy UD
    Int J Food Sci Nutr, 2021 Jun;72(4):470-477.
    PMID: 33032478 DOI: 10.1080/09637486.2020.1830263
    Hypertension is defined as the persistence of elevated blood pressure in the circulation system. The renin-angiotensin-aldosterone system is a major modulator of blood pressure. Among the risk factors of cardiovascular disease, hypertension is the most preventable and treatable, with drugs such as ACE inhibitors. Many ACE inhibitors are known to have undesirable side effects and hence, natural alternatives are being sought. Dietary polyphenols, particularly ellagitannins, are derived from plant products and are known to exhibit a variety of bioactivities. Geraniin, an ellagitannin has been shown to have antihypertensive activity in animal experiments. It is speculated that the metabolites of geraniin are responsible for its ACE inhibitory activity. We have performed in vitro ACE inhibition and in silico studies with geraniin and its metabolites (ellagic acid, urolithins). Our studies confirm that ellagic acid exhibited similar inhibitory potential to ACE as the positive control captopril.
    Matched MeSH terms: Antihypertensive Agents/pharmacology
  10. Fulltext Angiotensin receptor neprilysin inhibitor as a novel antihypertensive drug: Evidence from Asia and around the globe
    Lin DS, Wang TD, Buranakitjaroen P, Chen CH, Cheng HM, Chia YC, et al.
    J Clin Hypertens (Greenwich), 2021 03;23(3):556-567.
    PMID: 33305531 DOI: 10.1111/jch.14120
    Hypertension is a worldwide epidemic that continues to grow, with a subset of patients responding poorly to current treatment available. This is especially relevant in Asia, which constitutes 61% of the global population. Hypertension in Asia is a unique entity that is often salt-sensitive, nocturnal, and systolic predominant. Sacubitril/valsartan is a first-in-class angiotensin receptor neprilysin inhibitor that was first used in heart failure with reduced ejection fraction. Sacubitril inhibits neprilysin, a metallopeptidase that degrades natriuretic peptides (NPs). NPs exert sympatholytic, diuretic, natriuretic, vasodilatory, and insulin-sensitizing effects mostly via cyclic guanosine monophosphate (cGMP)-mediated pathways. As an antihypertensive agent, sacubitril/valsartan has outperformed angiotensin II receptor type 1 blockers (ARBs), with additional reductions of office systolic blood pressures ranging between 5 and 7 mmHg, in multiple studies in Asia and around the globe. The drug was well tolerated even in the elderly or those with chronic kidney disease. Its mechanisms of actions are particularly attractive for treatment of hypertension in Asia. Sacubitril/valsartan offers a novel, dual class, single-molecule property that may be considered as first-line antihypertensive therapy. Further investigations are needed to validate its safety for long-term use and to explore other potentials such as in the management of insulin resistance and obesity, which often coexist with hypertension in Asia.
    Matched MeSH terms: Antihypertensive Agents/pharmacology
  11. Fulltext Guidance on ambulatory blood pressure monitoring: A statement from the HOPE Asia Network
    Kario K, Hoshide S, Chia YC, Buranakitjaroen P, Siddique S, Shin J, et al.
    J Clin Hypertens (Greenwich), 2021 Mar;23(3):411-421.
    PMID: 33319412 DOI: 10.1111/jch.14128
    Hypertension is an important public health issue due to its association with a number of serious diseases, including cardiovascular disease and stroke. The importance of evaluating hypertension taking into account different blood pressure (BP) profiles and BP variability (BPV) is increasingly being recognized, and is particularly relevant in Asian populations given the specific features of hypertension in the region (including greater salt sensitivity and a high rate of nocturnal hypertension). Ambulatory BP monitoring (ABPM) is the gold standard for diagnosing hypertension and assessing 24-hour BP and provides data on several important parameters that cannot be obtained using any other form of BP measurement. In addition, ABPM parameters provide better information on cardio- and cerebrovascular risk than office BP. ABPM should be used in all patients with elevated BP, particularly those with unstable office or home BP, or who are suspected to have white-coat or masked hypertension. ABPM is also an important part of hypertension diagnosis and monitoring in high-risk patients. ABPM needs to be performed using a validated device and good practice techniques, and has a role both in hypertension diagnosis and in monitoring the response to antihypertensive therapy to ensure strict BP control throughout the 24-hour period. Use of ABPM in clinical practice may be limited by cost and accessibility, and practical education of physicians and patients is essential. The ABPM evidence and practice points in this document are based on the Hypertension Cardiovascular Outcome Prevention and Evidence (HOPE) Asia Network expert panel consensus recommendations for ABPM in Asia.
    Matched MeSH terms: Antihypertensive Agents/pharmacology
  12. Fulltext Relationship of an adherence score with blood pressure control status among patients with hypertension and their determinants: Findings from a nationwide blood pressure screening program
    Chia YC, Devaraj NK, Ching SM, Ooi PB, Chew MT, Chew BN, et al.
    J Clin Hypertens (Greenwich), 2021 03;23(3):638-645.
    PMID: 33586334 DOI: 10.1111/jch.14212
    This study aimed to examine the relationship of adherence with blood pressure (BP) control and its associated factors in hypertensive patients. This cross-sectional nationwide BP screening study was conducted in Malaysia from May to October 2018. Participants with self-declared hypertension completed the Hill-Bone Compliance to High Blood Pressure Therapy Scale (Hill-Bone CHBPTS) which assesses three important domains of patient behavior to hypertension management namely medication taking, appointment keeping and reduced salt intake. Lower scores indicate better compliance while higher scores indicate otherwise. Participant's body mass index and seated BP were measured based on standard measurement protocol. Determinants of adherence to treatment were analyzed using multiple linear regression. Out of 5167 screened subjects, 1705 were known hypertensives. Of these, 927 (54.4%) answered the Hill-Bone CHBPTS and were entered into analysis. The mean age was 59.0 ± 13.2 years, 55.6% were female and 42.2% were Malays. The mean Hill-Bone CHBPTS score was 20.4 ± 4.4 (range 14-47), and 52.1% had good adherence. The mean systolic BP and diastolic BP were 136.4 ± 17.9 and 80.6 ± 11.6 mmHg, respectively. BP was controlled in 58.3% of those with good adherence compared to 50.2% in those with poor adherence (p = .014). Based on multiple linear regression analysis, female gender (β = -0.72, 95% confidence interval [CI] -1.30, -0.15, p = .014), older age (β = -0.05, 95% CI -0.07, -0.03, p 
    Matched MeSH terms: Antihypertensive Agents/pharmacology
  13. 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
  14. Antihypertensive efficacy and safety of a standardized herbal medicinal product of Hibiscus sabdariffa and Olea europaea extracts (NW Roselle): A phase-II, randomized, double-blind, captopril-controlled clinical trial
    Elkafrawy N, Younes K, Naguib A, Badr H, Kamal Zewain S, Kamel M, et al.
    Phytother Res, 2020 Dec;34(12):3379-3387.
    PMID: 32725873 DOI: 10.1002/ptr.6792
    Hypertension is a public health concern that needs immediate attention upon diagnosis. The demand for natural alternatives is on the rise; Hibiscus sabdariffa and Olea europaea are traditionally used for hypertension management in Egypt. In this study, we aimed to investigate the antihypertensive efficacy and safety of two doses of an herbal product of Hibiscus sabdariffa calyxes and Olea europaea leaves (NW Roselle) in Egyptian patients with grade 1 essential hypertension. We equally randomized 134 patients to receive captopril 25 mg, low-dose NW Roselle, or high-dose NW Roselle BID for 8 weeks. No significant decrease was found in systolic blood pressure or diastolic blood pressure when we compared low-dose NW Roselle and high-dose NW Roselle to captopril (p > .05). In all groups, mean reduction in BP at 8 weeks was significant; 16.4/9.9 mmHg (p
    Matched MeSH terms: Antihypertensive Agents/pharmacology
  15. In vitro study and structure-activity relationship analysis of stilbenoid derivatives as powerful vasorelaxants: Discovery of new lead compound
    Chan SY, Loh YC, Oo CW, Yam MF
    Bioorg Chem, 2020 11;104:104239.
    PMID: 33142420 DOI: 10.1016/j.bioorg.2020.104239
    The development of vasorelaxant as the antihypertensive drug is important as it produces a rapid and direct relaxation effect on the blood vessel muscles. Resveratrol (RV), as the most widely studied stilbenoid and the lead compound, inducing the excellent vasorelaxation effect through the multiple signalling pathways. In this study, the in vitro vascular response of the synthesized trans-stilbenoid derivatives, SB 1-8e were primarily evaluated by employing the phenylephrine (PE)-precontracted endothelium-intact isolated aortic rings. Herein we report trans-3,4,4'-trihydroxystilbene (SB 8b) exhibited surprisingly more than 2-fold improvement to the maximal relaxation (Rmax) of RV. This article also highlights the characterization of the aromatic protons in terms of their unique splitting patterns in 1H NMR.
    Matched MeSH terms: Antihypertensive Agents/pharmacology*
  16. Resistant hypertension during antituberculosis treatment: how is rifampicin implicated?
    Lee SL, Lim WJ, Chai ST
    Med J Malaysia, 2020 09;75(5):591-593.
    PMID: 32918434
    A 67-year-old mental institute resident was treated for smear-positive pulmonary tuberculosis. His background history included chronic essential hypertension which was well-controlled with amlodipine 10mg daily. However, his blood pressure became suboptimal one week into antitubercular treatment, necessitating escalation of antihypertensive therapy up to six medications. Following completion of antitubercular treatment, his blood pressure improved markedly. The number of antihypertensives was able to be reduced to only two after a month. We postulate that rifampicin has attenuated the therapeutic effect of amlodipine via potent induction of hepatic CYP3A4 but the failure to control the blood pressure even with medications unrelated to cytochrome P450 pathways raises the spectre of an additional interaction.
    Matched MeSH terms: Antihypertensive Agents/pharmacology*
  17. Fulltext Cardiovascular Disease and Use of Renin-Angiotensin System Inhibitors in COVID-19
    Kow CS, Zaidi STR, Hasan SS
    Am J Cardiovasc Drugs, 2020 Jun;20(3):217-221.
    PMID: 32281055 DOI: 10.1007/s40256-020-00406-0
    There is ongoing debate on the safety of renin-angiotensin system (RAS) inhibitors in COVID-19. Recently published studies highlight a potential relationship between cardiovascular disease (CVD) and COVID-19. This article aims to summarize the evidence on the use of RAS inhibitors in CVD patients with COVID-19, focusing on safety issues of the RAS inhibitors and their relationship with COVID-19.
    Matched MeSH terms: Antihypertensive Agents/pharmacology
  18. New flavonoid-based compound synthesis strategy for antihypertensive drug development
    Loh YC, Chan SY, Tew WY, Oo CW, Yam MF
    Life Sci, 2020 May 15;249:117512.
    PMID: 32145305 DOI: 10.1016/j.lfs.2020.117512
    Hypertension is one of the leading causes of mortality in relation to the cardiovascular conditions and easily the most overlooked and poorly managed disease in mankind. With well over 200 drugs available in the market globally, there is still an urgency to search for antihypertensive alternatives due to the subpar efficacy and unwarranted side effects of the current choices. Present studies reported over 250 types of plant-derived compounds were being investigated for potential pharmacological effects on the vasculature in the last 3 decades. There were numerous literatures that claimed various compounds exhibiting vasorelaxant properties to a certain extent with low numbers of these compounds being successfully adapted into the current medicinal practice for treatment of hypertension. The issue is the scarcity of reviews that summarizes the discovery of this field and the lack of thorough comparison of these compounds to identify which of these vasodilators should be the next face of hypertension management. Thus, this review is aiming towards identifying the relationship between a major class of plant-derived compounds, flavonoid's activity as a vasodilator with their signalling pathways and their structural characteristics according to their vasorelaxant properties. Interestingly, we found that both nitric oxide and voltage-operated calcium channels pathways, and two of the flavonoid's structural characteristics play crucial roles in eliciting strong vasorelaxant effects. We have faith that the insights of this review will serve as a reference for those researching similar topics in the future and potentially lead to the development of more promising antihypertensive alternative.
    Matched MeSH terms: Antihypertensive Agents/pharmacology
  19. Blood pressure lowering effect and vascular activity of Phyllanthus niruri extract: The role of NO/cGMP signaling pathway and β-adrenoceptor mediated relaxation of isolated aortic rings
    Bello I, Usman NS, Dewa A, Abubakar K, Aminu N, Asmawi MZ, et al.
    J Ethnopharmacol, 2020 Mar 25;250:112461.
    PMID: 31830549 DOI: 10.1016/j.jep.2019.112461
    ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus niruri have a long history of use in the traditional treatment of various ailments including hypertension. Literature reports have indicated that it is a potent antihypertensive herbal medication used traditionally.

    AIM OF THE STUDY: This study was carried out to investigate the antihypertensive and vasodilatory activity of four solvents extracts of P. niruri namely; petroleum ether (PEPN), chloroform (CLPN), methanol (MEPN) and water (WEPN), with the aim of elucidating the mechanism of action and identifying the phytochemical constituents.

    MATERIALS AND METHODS: Male Spontaneous Hypertensive Rats (SHRs) were given oral gavage of P. niruri extract daily for two weeks and the blood pressure was recorded in vivo. We also determine the vasodilation effect of the extracts on rings of isolated thoracic aorta pre-contracted with phenylephrine (PE, 1 μM). Endothelium-intact or endothelium-denuded aorta rings were pre-incubated with various antagonists like 1H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 μM) and Methylene blue (MB 10 μM), sGC inhibitors; Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 10 μM) a nitric oxide synthase (NOS) inhibitor; atropine (10 μM), a cholinergic receptor blocker; indomethacin (10 μM), a cyclooxygenase inhibitor and various K+ channel blockers such as glibenclamide (10 μM) and tetraethyl ammonium (TEA 10 μM) for mechanism study.

    RESULTS: SHRs receiving P. niruri extracts showed a significant decrease in their blood pressure (BP) when compared to the baseline value, with PEPN being more potent. The extracts (0.125-4 mg/mL) also induced vasorelaxation on endothelium-intact aorta rings. PEPN elicited the most potent maximum relaxation effect (Rmax). Mechanism assessment of PEPN showed that its relaxation effect is significantly suppressed in endothelium-denuded aorta rings. Pre-incubation of aorta rings with atropine, L-NAME, ODQ, indomethacin, and propranolol also significantly attenuated its relaxation effect. Conversely, incubation with TEA and glibenclamide did not show a significant effect on PEPN-induced relaxation.

    CONCLUSION: This study indicates that the antihypertensive activity of P. niruri extract is mediated by vasoactive phytoconstituents that dilate the arterial wall via endothelium-dependent pathways and β-adrenoceptor activity which, in turn, cause vasorelaxation and reduce blood pressure.

    Matched MeSH terms: Antihypertensive Agents/pharmacology*
  20. 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*
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