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Recent Advances in the Genetics of Hypertension

Wei LK, Au A, Teh LK, Lye HS

Adv Exp Med Biol, 2017;956:561-581.
PMID: 27957710 DOI: 10.1007/5584_2016_75

Hypertension is a silent killer worldwide, caused by both genetic and environmental factors. Until now, genetic and genomic association studies of hypertension are reporting different degree of association on hypertension. Hence, it is essential to gather all the available information on the reported genetic loci and to determine if any biomarker(s) is/are significantly associated with hypertension. Current review concluded the potential biomarkers for hypertension, with regards to electrolyte and fluid transports, as well as sodium/potassium ions homeostasis, which are supported by the results of case-controls and meta-analyses.

Matched MeSH terms: Hypertension/physiopathology
Management of Patient Care in Hemodialysis While Focusing on Cardiovascular Disease Events and the Atypical Role of Hyper- and/or Hypotension: A Systematic Review

Khan A, Khan AH, Adnan AS, Syed Sulaiman SA, Gan SH, Khan I

Biomed Res Int, 2016;2016:9710965.
PMID: 27833921

Background. Hemodialysis related hemodynamic instability is a major but an underestimated issue. Moreover, cardiovascular events are the leading cause of morbidity and mortality associated with blood pressure in hemodialysis patients. However, there have been many controversies regarding the role and management of hyper- and/or hypotension during hemodialysis that needs to be addressed. Objective. To critically review the available published data on the atypical role of hyper- and/or hypotension in cardiovascular associated morbidity and mortality in patients on hemodialysis and to understand the discrepancies in this context. Methods. A comprehensive search of literature employing electronic as well as manual sources and screening 2783 papers published between Jan 1980 and Oct 2015 was conducted to collect, identify, and analyze relevant information through peer-reviewed research articles, systematic reviews, and other published works. The cardiovascular events, including accelerated atherosclerotic cardiovascular disease (ASCVD), stroke, heart failure, myocardial infarction, myocardial ischemia, and stress induced myocardial dysfunction, leading to death were considered relevant. Results. A total of 23 published articles met the inclusion criteria and were included for in-depth review and analysis to finalize a comprehensive systematic review article. All the studies showed a significant association between the blood pressure and cardiovascular disease events in hemodialysis patients. Conclusions. Both intradialytic hypertension/hypotension episodes are major risk factors for cardiovascular mortality with a high percentage of probable causality; however, clinicians are faced with a dilemma on how to evaluate blood pressure and treat this condition.

Matched MeSH terms: Hypertension/physiopathology*
Leptin in reproduction and hypertension in pregnancy

Singh H, Almabhouh FA, Alshaikhli HSI, Hassan MJM, Daud S, Othman R, et al.

Reprod Fertil Dev, 2024 Jul;36.
PMID: 39038160 DOI: 10.1071/RD24060

Leptin has important roles in numerous physiological functions, including those in the regulation of energy balance, and in immune and reproductive systems. However, in the recent years, evidence has implicated it in a number of obesity-related diseases, where its concentrations in serum are significantly elevated. Elevated serum leptin concentrations and increased placental leptin secretion have been reported in women with hypertensive disorders of pregnancy. Whether leptin is responsible for this disorder remains to be established. Leptin injections in healthy rats and mice during pregnancy result in endothelial activation, increased blood pressure and proteinuria. A potential role for leptin in the pathogenesis of pre-eclampsia is hypothesised, particularly in women who are overweight or obese where serum leptin concentrations are often elevated. This review summarises pertinent information in the literature on the role of leptin in puberty, pregnancy, and hypertensive disorders of pregnancy. In particular, the possible mechanism that may be involved in leptin-induced increase in blood pressure and proteinuria during pregnancy and the potential role of marinobufagenin in this disease entity. We hypothesise a significant role for oxidative stress in this, and propose a conceptual framework on the events that lead to endothelial activation, raised blood pressure and proteinuria following leptin administration.

Matched MeSH terms: Hypertension/physiopathology
Fulltext Influence of angiotensin II on the gut microbiome: modest effects in comparison to experimental factors

R Muralitharan R, Nakai ME, Snelson M, Zheng T, Dinakis E, Xie L, et al.

Cardiovasc Res, 2024 Sep 02;120(10):1155-1163.
PMID: 38518247 DOI: 10.1093/cvr/cvae062

AIMS: Animal models are regularly used to test the role of the gut microbiome in hypertension. Small-scale pre-clinical studies have investigated changes to the gut microbiome in the angiotensin II hypertensive model. However, the gut microbiome is influenced by internal and external experimental factors, which are not regularly considered in the study design. Once these factors are accounted for, it is unclear if microbiome signatures are reproduceable. We aimed to determine the influence of angiotensin II treatment on the gut microbiome using a large and diverse cohort of mice and to quantify the magnitude by which other factors contribute to microbiome variations.
METHODS AND RESULTS: We conducted a retrospective study to establish a diverse mouse cohort resembling large human studies. We sequenced the V4 region of the 16S rRNA gene from 538 samples across the gastrointestinal tract of 303 male and female C57BL/6J mice randomized into sham or angiotensin II treatment from different genotypes, diets, animal facilities, and age groups. Analysing over 17 million sequencing reads, we observed that angiotensin II treatment influenced α-diversity (P = 0.0137) and β-diversity (i.e. composition of the microbiome, P < 0.001). Bacterial abundance analysis revealed patterns consistent with a reduction in short-chain fatty acid producers, microbial metabolites that lower blood pressure. Furthermore, animal facility, genotype, diet, age, sex, intestinal sampling site, and sequencing batch had significant effects on both α- and β-diversity (all P < 0.001). Sampling site (6.8%) and diet (6%) had the largest impact on the microbiome, while angiotensin II and sex had the smallest effect (each 0.4%).
CONCLUSION: Our large-scale data confirmed findings from small-scale studies that angiotensin II impacted the gut microbiome. However, this effect was modest relative to most of the other factors studied. Accounting for these factors in future pre-clinical hypertensive studies will increase the likelihood that microbiome findings are replicable and translatable.

Matched MeSH terms: Hypertension/physiopathology
Fulltext Morning surge in blood pressure and blood pressure variability in Asia: Evidence and statement from the HOPE Asia Network

Sogunuru GP, Kario K, Shin J, Chen CH, Buranakitjaroen P, Chia YC, et al.

J Clin Hypertens (Greenwich), 2019 02;21(2):324-334.
PMID: 30525279 DOI: 10.1111/jch.13451

Hypertension is a major risk factor for cardiovascular and cerebrovascular diseases. To effectively prevent end-organ damage, maintain vascular integrity and reduce morbidity and mortality, it is essential to decrease and adequately control blood pressure (BP) throughout each 24-hour period. Exaggerated early morning BP surge (EMBS) is one component of BP variability (BPV), and has been associated with an increased risk of stroke and cardiovascular events, independently of 24-hour average BP. BPV includes circadian, short-term and long-term components, and can best be documented using out-of-office techniques such as ambulatory and/or home BP monitoring. There is a large body of evidence linking both BPV and EMBS with increased rates of adverse cardio- and cerebrovascular events, and end-organ damage. Differences in hypertension and related cardiovascular disease rates have been reported between Western and Asian populations, including a higher rate of stroke, higher prevalence of metabolic syndrome, greater salt sensitivity and more common high morning and nocturnal BP readings in Asians. This highlights a need for BP management strategies that take into account ethnic differences. In general, long-acting antihypertensives that control BP throughout the 24-hour period are preferred; amlodipine and telmisartan have been shown to control EMBS more effectively than valsartan. Home and ambulatory BP monitoring should form an essential part of hypertension management, with individualized pharmacotherapy to achieve optimal 24-hour BP control particularly the EMBS and provide the best cardio- and cerebrovascular protection. Future research should facilitate better understanding of BPV, allowing optimization of strategies for the detection and treatment of hypertension to reduce adverse outcomes.

Matched MeSH terms: Hypertension/physiopathology
Fulltext Effects of weight loss intervention on body composition and blood pressure among overweight and obese women: findings from the MyBFF@home study

Fazliana M, Liyana AZ, Omar A, Ambak R, Mohamad Nor NS, Shamsudin UK, et al.

BMC Womens Health, 2018 07 19;18(Suppl 1):93.
PMID: 30066641 DOI: 10.1186/s12905-018-0592-2

BACKGROUND: Obesity is related to the increased incidence of hypertension and in healthy individuals, blood pressure changes with age and body mass. The aims of this paper were to evaluate the effectiveness of the weight loss intervention on body composition and blood pressure, and to evaluate the relationship between these factors among housewives in the MyBFF@home study.
METHODS: MyBFF@home intervention was a quasi-experimental study which involved 328 overweight and obese housewives aged 18-59 years old (Control group: 159, Intervention group: 169). Data of the control and intervention group (pre and post intervention who completed the body composition and blood pressure measurements were analysed. Body compositions were measured using the Body Impedance Analyser (InBody 720) and blood pressure (Systolic and Diastolic) was taken using the blood pressure monitoring device (Omron HEM 907) at baseline, 6 month and 12 month. Data analyses (Pearson's correlation test and ANOVA) were performed and analysed using SPSS Statistics for Windows, version 22.0.
RESULTS: Visceral fat area, fat mass and body fat percentage, were all significantly decreased in the intervention group compared to the control group after 6 month intervention (p

Matched MeSH terms: Hypertension/physiopathology*
Fulltext The HOPE Asia Network consensus on blood pressure measurements corresponding to office measurements: Automated office, home, and ambulatory blood pressures

Shin J, Wang JG, Chia YC, Kario K, Chen CH, Cheng HM, et al.

J Clin Hypertens (Greenwich), 2024 Dec;26(12):1351-1361.
PMID: 37878534 DOI: 10.1111/jch.14729

For adopting recently introduced hypertension phenotypes categorized using office and out of office blood pressure (BP) for the diagnosis of hypertension and antihypertension drug therapy, it is mandatory to define the corresponding out of office BP with the specific target BP recommended by the major guidelines. Such conditions include white-coat hypertension (WCH), masked hypertension (MH), white-coat uncontrolled hypertension (WUCH), and masked uncontrolled hypertension (MUCH). Here, the authors review the relevant literature and discuss the related issue to facilitate the use of corresponding BPs for proper diagnosis of WCH, MH, WUCH, and MUCH in the setting of standard target BP as well as intensive target BP. The methodology of deriving the corresponding BP has evolved from statistical methods such as standard deviation, percentile value, and regression to an outcome-based approach using pooled international cohort study data and comparative analysis in randomized clinical trials for target BPs such as the SPRINT and STEP studies. Corresponding BPs to 140/90 and 130/80 mm Hg in office BP is important for safe and strict achievement of intensive BP targets. The corresponding home, daytime, and 24-h BPs to 130/80 mm Hg in office BP are 130/80, 130/80, and 125/75 mm Hg, respectively. However, researchers have found some discrepancies among the home corresponding BPs. As tentative criterion for de-escalation of antihypertensive therapy as shown in European guidelines was 120 mm Hg in office BP, corresponding home, daytime, and 24-h systolic BPs to 120 mm Hg in office systolic BP are 120, 120, and 115 mm Hg, respectively.

Matched MeSH terms: Masked Hypertension/physiopathology
2005 Young Investigator's Award Winner: Assessment of diastolic function in newly diagnosed hypertensives

Masliza M, Daud SM, Khalid Y

Ann Acad Med Singap, 2005 Dec;34(11):684-5.
PMID: 16453041

INTRODUCTION: The prevalence and severity of diastolic dysfunction (DD) among newly diagnosed hypertensives (NDHT) is not fully established. The aim of this study was to evaluate left ventricular diastolic function (LVDF) in patients with NDHT.
MATERIALS AND METHODS: This study involved 396 subjects (198 NDHT, age and gender matched 198 normotensives; age, 30 to 50 years). Parameters of LVDF included Doppler-echocardiographic measurements of peak early (E) and late (A) diastolic velocities, E-wave deceleration time (DT) and isovolumetric relaxation time (IVRT). E/A ratio of <1 was taken as an indicative of DD.
RESULTS: Patients with NDHT had reduced E/A ratio (1.27 +/- 0.41 vs 1.37 +/- 0.35, P <0.001) and shortened DT (180.0 +/- 40.0 ms vs 190.0 +/- 30.0 ms, P = 0.025). The peak A velocity and IVRT were increased in the NDHT group [(62.73 +/- 13.82 ms vs 58.26 +/- 12.40 ms, P = 0.002) and (90.0 +/- 20.0 ms vs 80.0 +/- 10.0 ms, P <0.001), respectively]. Peak E velocity was similar in both groups. The prevalence of DD was increased in the NDHT group, 18.6% (32) vs 3.4% (6), P <0.001. Of the 32 NDHT subjects who had DD, 84.4% (27) had no left ventricular hypertrophy (LVH) and 15.7% (5) had LVH. Diastolic function was negatively correlated with age, body mass index, systolic blood pressure, diastolic blood pressure and left ventricular mass index.
CONCLUSION: Impairment in LVDF occurs in NDHT which may precede structural abnormalities. Hypertension, obesity, older age and LVH are associated with worsening of diastolic function.

Matched MeSH terms: Hypertension/physiopathology*
Mean target intraocular pressure and progression rates in chronic angle-closure glaucoma

Sharmini AT, Yin NY, Lee SS, Jackson AL, Stewart WC

J Ocul Pharmacol Ther, 2009 Feb;25(1):71-5.
PMID: 19232007 DOI: 10.1089/jop.2008.0061

The aim of this study was to evaluate risk factors for progression in chronic angle-closure glaucoma (CACG) patients.

Matched MeSH terms: Ocular Hypertension/physiopathology*
Fulltext Microalbuminuria prevalence study in hypertensive type 2 diabetic patients in Malaysia

Kong NC, Chia YC, Khalid BA, Juwita S, Samiah Yasmin AK, Yap LY, et al.

Med J Malaysia, 2006 Oct;61(4):457-65.
PMID: 17243524 MyJurnal

Microalbuminuria is the earliest indicator of diabetic kidney disease and generalised vascular endothelial dysfunction. The Microalbuminuria Prevalence (MAP) Study was carried out to assess the prevalence of macroalbuminuria, microalbuminuria and normoalbuminuria in Asian hypertensive patients with type 2 diabetes on usual care. This paper presents a subanalysis of data from patients in Malaysia. In 733 analysed patients, the prevalence of macroalbuminuria and microalbuminuria was 15.7% and 39.7%, respectively. The high prevalence of diabetic nephropathy in these high-risk patients is a cause for concern, and the Malaysian Health Care system should be prepared for a pandemic of end-stage renal disease due to diabetic nephropathy.

Study site: six medical centres in Kuala Lumpur, Kota Bharu,
Kuching and Kota Kinabalu

Matched MeSH terms: Hypertension/physiopathology
Blood pressure regulation by the kallikrein-kinin system

Sharma JN, Uma K, Noor AR, Rahman AR

Gen. Pharmacol., 1996 Jan;27(1):55-63.
PMID: 8742494

1. The kallikrein-kinin system has a significant role in regulating arterial blood pressure. 2. Reduced formation of the kinin compontents may cause hypertensive diseases. This is because of the fact that this system is responsible for vasodilatation, reduction in total peripheral resistance, natriuresis, diuresis, increasing renal blood flow and releasing various vasodilator agents. 3. Reduced kinin-kallikrein generation in hypertensive subjects may also be associated with genetic and environmental defects. 4. The kallikrein-kinin system when administered to hypertensive patients can lower their raised blood pressure to normotensive levels. 5. The mode of action of angiotensin-converting enzyme inhibitors principally may be dependent on the kinin system protection.

Matched MeSH terms: Hypertension/physiopathology*
Fulltext Dose requirement and effect of nicardipine on lipid profile in mild to moderate essential hypertensives

Tariq AR, Maheendran K, Kamsiah J, Christina P

Med J Malaysia, 1992 Sep;47(3):182-9.
PMID: 1491643

Twenty eight patients who satisfied the entry criteria and had completed an initial 2 weeks treatment with placebo were titrated fortnightly with doses of Nicardipine ranging from 30 mg to 90 mg daily in two or three divided doses. Nicardipine treatment significantly reduced blood pressures both in the supine and standing positions (p < 0.0004) when compared with placebo treatment. Heart rates however did not change significantly. Forty six percent (13/28) of patients on 20 mg twice daily, 25% (7/28) on 10 mg three times daily, 18% (5/28) of patients on 20 mg three times daily and 11% (3/28) on 30 mg three times daily achieved supine diastolic blood pressures < 90 mm Hg. Nicardipine treatment at 16 weeks and at 24 weeks did not significantly alter the lipid profile when compared to the end of placebo treatment period. No other biochemical abnormalities were reported during the study period. Except for 2 cases of mild pedal oedema and 2 cases of transient headaches, no serious side-effects were encountered.

Matched MeSH terms: Hypertension/physiopathology
Suppression of hypotensive responses of captopril and enalapril by the kallikrein inhibitor aprotinin in spontaneously hypertensive rats

Sharma JN, Amrah SS, Noor AR

Pharmacology, 1995 Jun;50(6):363-9.
PMID: 7568335

The present investigation evaluated the effects of aprotinin, an inhibitor of kallikrein, on blood pressure responses, heart rate, and duration of hypotension induced by acute administration of captopril and enalapril (angiotensin-converting enzyme inhibitors) in anaesthetized spontaneously hypertensive rats. Captopril (20 mg/kg) and enalapril (20 mg/kg) administered intravenously caused a significant (p < 0.001) fall in systolic and diastolic blood pressures in the absence of aprotinin. In contrast, captopril (20 mg/kg) and enalapril (20 mg/kg) failed (p > 0.05) to cause a fall in systolic and diastolic blood pressures in the presence of aprotinin (2 mg/kg). Captopril and enalapril were able to significantly reduce the heart rate (p < 0.05 and p < 0.001) in the presence as well as in the absence of aprotinin. The duration of hypotension produced by captopril and enalapril was abolished significantly (p < 0.001) in the presence of aprotinin. These findings may suggest that captopril and enalapril caused hypotension via the kallikrein pathway, since the kallikrein inhibitor aprotinin can antagonize the hypotensive responses of these agents. Thus, kallikrein may be an independent mediator in the regulation of blood pressure.

Matched MeSH terms: Hypertension/physiopathology
Fulltext Blood pressure in acute intracerebral haemorrhage

Rasool AH, Rahman AR, Choudhury SR, Singh RB

J Hum Hypertens, 2004 Mar;18(3):187-92.
PMID: 14973513 DOI: 10.1038/sj.jhh.1001647

Stroke is one of the leading causes of death worldwide, and spontaneous bleeding into the brain parenchyma, intracerebral haemorrhage (ICH), is a stroke subtype associated with high morbidity and mortality. Overall, it comprises about 15% of all stroke in Caucasians, this figure being much higher in Asians and black people. Blood pressure (BP) appears to play an important role in this disease. We have reviewed available literature on the relationship of BP to the occurrence of primary and secondary ICH, the association of BP levels measured early after stroke with prognosis and complications, and evidence about the effects of early BP lowering treatments on post-stroke outcomes. BP appears to be an important risk factor for primary and secondary ICH. In addition, high BP early after ICH may be detrimental to outcome, possibly contributing to complications such as rebleeding and haematoma enlargement. Few data are available about the effects of early lowering of BP on outcome after ICH with no reliable trial yet conducted. Proper randomised trials are required to establish the effect of early lowering of BP on outcome after ICH.

Matched MeSH terms: Hypertension/physiopathology
Effect of melatonin supplementation and cross-fostering on renal glutathione system and development of hypertension in spontaneously hypertensive rats

Siew-Keah L, Sundaram A, Sirajudeen KN, Zakaria R, Singh HJ

J Physiol Biochem, 2014 Mar;70(1):73-9.
PMID: 23975651 DOI: 10.1007/s13105-013-0282-3

Antenatal and postnatal environments are hypothesised to influence the development of hypertension. This study investigates the synergistic effect of cross-fostering and melatonin supplementation on the development of hypertension and renal glutathione system in spontaneously hypertensive rats (SHR). In one experiment, 1-day-old male SHR pups were fostered to either SHR (shr-SHR) or Wistar-Kyoto rats, (shr-WKY). In a concurrent experiment, SHR dams were given melatonin in drinking water (10 mg/kg body weight) from day 1 of pregnancy. Immediately following delivery, 1-day-old male pups were fostered either to SHR (Mel-shr-SHR) or WKY (Mel-shr-WKY) dams receiving melatonin supplementation until weaning on day 21. Upon weaning, melatonin supplementation was continued to these pups until the age of 16 weeks. Systolic blood pressures (SBP) were recorded at the age of 4, 6, 8, 12 and 16 weeks. Renal antioxidant activities were measured. Mean SBP of shr-WKY, Mel-shr-SHR and Mel-shr-WKY was significantly lower than that in shr-SHR until the age of 8 weeks. At 12 and 16 weeks of age, mean SBP of Mel-shr-WKY was lower than those in non-treated shr-SHR and shr-WKY pups but was not significantly different from that in Mel-shr-SHR. Renal glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities were significantly higher in Mel-shr-SHR and Mel-shr-WKY at 16 weeks of age. It appears that combination of cross-fostering and melatonin supplementation exerts no synergistic effect on delaying the rise in blood pressure in SHR. The elevated GPx and GST activities are likely to be due to the effect of melatonin supplementation.

Matched MeSH terms: Hypertension/physiopathology
Fulltext Mid-term impact of home-based follow-up care on health-related quality of life of hypertensive patients at a teaching hospital in Ilorin, Nigeria

Bolarinwa OA, Juni MH, Nor Afiah MZ, Salmiah MS, Akande TM

Niger J Clin Pract, 2019 Jan;22(1):69-78.
PMID: 30666023 DOI: 10.4103/njcp.njcp_246_17

Background: Health-related quality of life (HRQoL) is an important clinical outcome assessment in hypertension management, given the lifelong (chronicity) nature and the need for daily self-management for hypertensive patents. Of some of the studies that implemented home-based interventions on hypertension globally, the HRQoL is rarely used as a primary outcome measure. This study developed, implemented, and assessed the impact of home-based follow-up care (HBFC) on HRQoL of hypertensive patients attending outpatients' clinics in Ilorin, Nigeria.
Materials and Methods: A total of 149 and 150 patients were randomized to intervention and usual care (control) groups, respectively. A 12-month task-shifting (nurse-driven) HBFC intervention was administered to intervention group. The mid-term impact of intervention on HRQoL was assessed after 6 months intervention. Data were analyzed with intention-to-treat principle. Treatment effects were measured with the t-tests, analysis of covariance, and multivariate analysis of covariance analysis. Significant levels were set at P < 0.05 and 95% confidence interval.
Results: The between-group treatment effect was not statistically significant (P > 0.05), whereas the within-group treatment effects were statistically significant for both the intervention and control arms (P < 0.05) at 6 months. After controlling for age and baseline HRQoL, the intervention group had an improved physical component of HRQoL than the control group. The intervention group also had statistically significant improvement in blood pressure control, medication adherence, and symptom counts (P < 0.05).
Conclusion: The HBFC intervention for hypertensive patients impacted positively on physical component of HRQoL after controlling for baseline HRQoL and age of the patients at 6 months post-intervention.

Matched MeSH terms: Hypertension/physiopathology
Prevalence and Risk Factors of Hypertension in the Vietnamese Elderly

Bui Van N, Vo Hoang L, Bui Van T, Anh HNS, Minh HT, Do Nam K, et al.

High Blood Press Cardiovasc Prev, 2019 Jun;26(3):239-246.
PMID: 31020550 DOI: 10.1007/s40292-019-00314-8

INTRODUCTION: Hypertension (HT) is considered as a major determinant of cardiovascular complications. However, few studies have addressed HT prevalence among adults aged 60 years and older in the northern mountainous region of Vietnam.
AIM: To determine the prevalence of HT and its risk factors in the elderly in that area.
METHODS: A cross-sectional study was conducted in a study area in the northern of Vietnam. We interviewed 354 adults aged 60 years or over who were randomly selected, and then measured their blood pressure.
RESULTS: The overall HT prevalence was 62.15%. The isolated systolic hypertension (ISH) prevalence was 22.88%. There was a slight decrease in the proportion of HT by stage 1, stage 2 and stage 3 respectively. The univariate and multivariate logistic regression analysis indicated some risk factors for HT including age groups, body mass index (BMI) and waist-hip ratio (WHR) (p

Matched MeSH terms: Hypertension/physiopathology
Microbial Peer Pressure: The Role of the Gut Microbiota in Hypertension and Its Complications

Muralitharan RR, Jama HA, Xie L, Peh A, Snelson M, Marques FZ

Hypertension, 2020 12;76(6):1674-1687.
PMID: 33012206 DOI: 10.1161/HYPERTENSIONAHA.120.14473

There is increasing evidence of the influence of the gut microbiota on hypertension and its complications, such as chronic kidney disease, stroke, heart failure, and myocardial infarction. This is not surprising considering that the most common risk factors for hypertension, such as age, sex, medication, and diet, can also impact the gut microbiota. For example, sodium and fermentable fiber have been studied in relation to both hypertension and the gut microbiota. By combining second- and, now, third-generation sequencing with metabolomics approaches, metabolites, such as short-chain fatty acids and trimethylamine N-oxide, and their producers, have been identified and are now known to affect host physiology and the cardiovascular system. The receptors that bind these metabolites have also been explored with positive findings-examples include known short-chain fatty acid receptors, such as G-protein coupled receptors GPR41, GPR43, GPR109a, and OLF78 in mice. GPR41 and OLF78 have been shown to have inverse roles in blood pressure regulation, whereas GPR43 and GPR109A have to date been demonstrated to impact cardiac function. New treatment options in the form of prebiotics (eg, dietary fiber), probiotics (eg, Lactobacillus spp.), and postbiotics (eg, the short-chain fatty acids acetate, propionate, and butyrate) have all been demonstrated to be beneficial in lowering blood pressure in animal models, but the underlying mechanisms remain poorly understood and translation to hypertensive patients is still lacking. Here, we review the evidence for the role of the gut microbiota in hypertension, its risk factors, and cardiorenal complications and identify future directions for this exciting and fast-evolving field.

Matched MeSH terms: Hypertension/physiopathology*
Therapeutic Implications of Nitrite in Hypertension

Ling WC, Mustafa MR, Murugan DD

J Cardiovasc Pharmacol, 2020 02;75(2):123-134.
PMID: 31651673 DOI: 10.1097/FJC.0000000000000771

Nitrite, an anion produced from the oxidative breakdown of nitric oxide (NO), has traditionally been viewed as an inert molecule. However, this dogma has been challenged with the findings that nitrite can be readily reduced to NO under pathological conditions, hence representing a physiologically relevant storage reservoir of NO either in the blood or tissues. Nitrite administration has been demonstrated to improve myocardial function in subjects with heart failure and to lower the blood pressure in hypertensive subjects. Thus, extensive amount of work has since been carried out to investigate the therapeutic potential of nitrite in treating cardiovascular diseases, especially hypertension. Studies done on several animal models of hypertension have demonstrated the efficacy of nitrite in preventing and ameliorating the pathological changes associated with the disease. This brief review of the current findings aims to re-evaluate the use of nitrite for the treatment of hypertension and in particular to highlight its role in improving endothelial function.

Matched MeSH terms: Hypertension/physiopathology
Effect of blood pressure on the retinal vasculature in a multi-ethnic Asian population

Jeganathan VS, Sabanayagam C, Tai ES, Lee J, Sun C, Kawasaki R, et al.

Hypertens Res, 2009 Nov;32(11):975-82.
PMID: 19713968 DOI: 10.1038/hr.2009.130

Blood pressure has a significant effect on retinal arterioles. There are few data on whether this effect varies by race/ethnicity. We examined the relationship of blood pressure and retinal vascular caliber in a multi-ethnic Asian population. The study is population-based and cross sectional in design. A total of 3749 Chinese, Malay and Indian participants aged > or =24 years residing in Singapore were included in the study. Retinal vascular caliber was measured using a computer program from digital retinal photographs. The associations of retinal vascular caliber with blood pressure and hypertension in each racial/ethnic group were analyzed. The main outcome measures are retinal arteriolar caliber and venular caliber. The results show that retinal arterioles were narrower in persons with uncontrolled/untreated hypertension (140.0 microm) as compared with persons with controlled hypertension (142.1 microm, P=0.0001) and those with no hypertension (146.0 microm, P<0.0001). On controlling for age, gender, body mass index, lipids and smoking, each 10 mm Hg increase in mean arterial blood pressure was associated with a 3.1 microm decrease in arteriolar caliber (P<0.0001), with a similar magnitude seen in all three racial/ethnic groups: 3.1 microm in Chinese, 2.8 microm in Malays and 3.2 microm in Indians (P<0.0001 for all). Each 10 mm Hg increase in mean arterial blood pressure was associated with a 1.8 microm increase in venular caliber (P<0.0001); furthermore, the magnitude of this effect was similar across the three racial/ethnic groups. The effect of blood pressure on the retinal vasculature was similar across three major racial/ethnic groups in Asia.

Matched MeSH terms: Hypertension/physiopathology

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