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Micromethod for the measurement of renin activity

Gan EK

Med J Malaysia, 1976 Jun;30(4):306-11.
PMID: 979734
Matched MeSH terms: Renin/analysis*; Renin/blood
Renin-angiotensin-aldosterone: An inclusive, an invigorative, an interactive and an interminable system

Balakumar P, Anand-Srivastava MB, Jagadeesh G

Pharmacol Res, 2017 11;125(Pt A):1-3.
PMID: 28711403 DOI: 10.1016/j.phrs.2017.07.003
Matched MeSH terms: Renin/metabolism*; Renin-Angiotensin System/physiology*
Fulltext Who should be screened for primary aldosteronism? A comprehensive review of current evidence

Huang WC, Lin YH, Wu VC, Chen CH, Siddique S, Chia YC, et al.

J Clin Hypertens (Greenwich), 2022 Sep;24(9):1194-1203.
PMID: 36196469 DOI: 10.1111/jch.14558

Arterial hypertension is a major risk factor for cardiovascular disease. The prevalence of primary aldosteronism (PA) ranges from 5% to 10% in the general hypertensive population and is regarded as one of the most common causes of secondary hypertension. There are two major causes of PA: bilateral adrenal hyperplasia and aldosterone-producing adenoma. The diagnosis of PA comprises screening, confirmatory testing, and subtype differentiation. The Endocrine Society Practice Guidelines for the diagnosis and treatment of PA recommends screening of patients at an increased risk of PA. These categories include patients with stage 2 and 3 hypertension, drug-resistant hypertension, hypertensive with spontaneous or diuretic-induced hypokalemia, hypertension with adrenal incidentaloma, hypertensive with a family history of early onset hypertension or cerebrovascular accident at a young age, and all hypertensive first-degree relatives of patients with PA. Recently, several studies have linked PA with obstructive sleep apnea and atrial fibrillation unexplained by structural heart defects and/or other conditions known to cause the arrhythmia, which may be partly responsible for the higher rates of cardiovascular and cerebrovascular accidents in patients with PA. The aim of this review is to discuss which patients should be screened for PA, focusing not only on well-established guidelines but also on additional groups of patients with a potentially higher prevalence of PA, as has been reported in recent research.

Matched MeSH terms: Renin
Fulltext Do the Meta-Analyses Provide a Clean Bill of Health to the Use of Renin-angiotensin System Inhibitors in Coronavirus Disease 2019 (COVID-19)?

Kow CS, Hasan SS

Clin Infect Dis, 2021 07 01;73(1):164-165.
PMID: 32770237 DOI: 10.1093/cid/ciaa1167
Matched MeSH terms: Renin-Angiotensin System*
Fulltext Influence and implications of the renin-angiotensin-aldosterone system in obstructive sleep apnea: An updated systematic review and meta-analysis

Loh HH, Lim QH, Chai CS, Goh SL, Lim LL, Yee A, et al.

J Sleep Res, 2023 Feb;32(1):e13726.
PMID: 36104933 DOI: 10.1111/jsr.13726

Obstructive sleep apnea is a chronic, sleep-related breathing disorder, which is an independent risk factor for cardiovascular disease. The renin-angiotensin-aldosterone system regulates salt and water homeostasis, blood pressure, and cardiovascular remodelling. Elevated aldosterone levels are associated with excess morbidity and mortality. We aimed to analyse the influence and implications of renin-angiotensin-aldosterone system derangement in individuals with and without obstructive sleep apnea. We pooled data from 20 relevant studies involving 2828 participants (1554 with obstructive sleep apnea, 1274 without obstructive sleep apnea). The study outcomes were the levels of renin-angiotensin-aldosterone system hormones, blood pressure and heart rate. Patients with obstructive sleep apnea had higher levels of plasma renin activity (pooled wmd+ 0.25 [95% confidence interval 0.04-0.46], p = 0.0219), plasma aldosterone (pooled wmd+ 30.79 [95% confidence interval 1.05-60.53], p = 0.0424), angiotensin II (pooled wmd+ 5.19 [95% confidence interval 3.11-7.27], p renin levels) when studies involving patients with resistant hypertension were removed. Sub-group analysis demonstrated that levels of angiotensin II were significantly higher only among the Asian population with obstructive sleep apnea compared with those without obstructive sleep apnea. Body mass index accounted for less than 10% of the between-study variance in elevation of the renin-angiotensin-aldosterone system parameters. Patients with obstructive sleep apnea have higher levels of renin-angiotensin-aldosterone system hormones, blood pressure and heart rate compared with those without obstructive sleep apnea, which remains significant even among patients without resistant hypertension.

Matched MeSH terms: Renin; Renin-Angiotensin System/physiology
The effect of vitamin D treatment on clinical and biochemical outcomes of primary aldosteronism

Ismail NA, Kamaruddin NA, Azhar Shah S, Sukor N

Clin Endocrinol (Oxf), 2020 06;92(6):509-517.
PMID: 32073675 DOI: 10.1111/cen.14177

INTRODUCTION: Primary aldosteronism (PA) contributed to the cardiovascular disease and metabolic alterations independent of the blood pressure level. Evidence exists that aldosterone excess also affects calcium and mineral homeostasis. PA subjects have been shown to have greater prevalence of vitamin D deficiency. However, the impact of vitamin D treatment in this population has never been assessed.
OBJECTIVE: This study aimed to evaluate the effect of vitamin D treatment on clinical and biochemical outcomes of PA patients.
METHODS: Two hundred forty hypertensive subjects were screened, 31 had positive ARR, and 17 patients with newly confirmed PA following positive confirmatory test that has not been subjected for definitive treatment were enrolled. Clinical parameter (blood pressure) and biochemical parameters (renal profile, plasma aldosterone concentration, plasma renin activity, serum calcium, vitamin D, intact parathyroid hormone, 24-hour urinary calcium) were measured at baseline and 3 months of treatment with Bio-D3 capsule. Primary outcomes were the changes in the blood pressure and biochemical parameters.
RESULTS: About 70% of our PA subjects have low vitamin D levels at baseline. Three months following treatment, there were significant: (a) improvement in 25(OH)D levels; (b) reduction in systolic blood pressure and plasma aldosterone concentration; and (c) improvement in the eGFR. The vitamin D deficient subgroup has the greatest magnitude of the systolic blood pressure reduction following treatment.
CONCLUSIONS: This study demonstrated significant proportion of PA patients has vitamin D insufficiency. Vitamin D treatment improves these interrelated parameters possibly suggesting interplay between vitamin D, aldosterone, renal function and the blood pressure.

Matched MeSH terms: Renin
International multicenter survey on screening and confirmatory testing in primary aldosteronism

Naruse M, Murakami M, Katabami T, Kocjan T, Parasiliti-Caprino M, Quinkler M, et al.

Eur J Endocrinol, 2023 Jan 10;188(1).
PMID: 36726325 DOI: 10.1093/ejendo/lvac002

OBJECTIVE: Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Although clinical practice guidelines recommend a diagnostic process, details of the steps remain incompletely standardized.
DESIGN: In the present SCOT-PA survey, we have investigated the diversity of approaches utilized for each diagnostic step in different expert centers through a survey using Google questionnaires. A total of 33 centers from 3 continents participated.
RESULTS: We demonstrated a prominent diversity in the conditions of blood sampling, assay methods for aldosterone and renin, and the methods and diagnostic cutoff for screening and confirmatory tests. The most standard measures were modification of antihypertensive medication and sitting posture for blood sampling, measurement of plasma aldosterone concentration (PAC) and active renin concentration by chemiluminescence enzyme immunoassay, a combination of aldosterone-to-renin ratio with PAC as an index for screening, and saline infusion test in a seated position for confirmatory testing. The cutoff values for screening and confirmatory testing showed significant variation among centers.
CONCLUSIONS: Diversity of the diagnostic steps may lead to an inconsistent diagnosis of PA among centers and limit comparison of evidence for PA between different centers. We expect the impact of this diversity to be most prominent in patients with mild PA. The survey raises 2 issues: the need for standardization of the diagnostic process and revisiting the concept of mild PA. Further standardization of the diagnostic process/criteria will improve the quality of evidence and management of patients with PA.

Matched MeSH terms: Renin
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: Renin-Angiotensin System*
Fulltext Effects of Angiotensin II Receptor Blockers on the Risk of Mortality in Patients with COVID-19: An Updated Systematic Review and Meta-analysis of Randomized Trials

Kow CS, Ramachandram DS, Hasan SS

Am J Hypertens, 2022 Aug 01;35(8):763-764.
PMID: 35657802 DOI: 10.1093/ajh/hpac070
Matched MeSH terms: Renin-Angiotensin System/drug effects
Fulltext 20-Hydroxyeicosatetraenoic acid (20-HETE): Bioactions, receptors, vascular function, cardiometabolic disease and beyond

Pascale JV, Wolf A, Kadish Y, Diegisser D, Kulaprathazhe MM, Yemane D, et al.

Adv Pharmacol, 2023;97:229-255.
PMID: 37236760 DOI: 10.1016/bs.apha.2023.01.002

Vascular function is dynamically regulated and dependent on a bevy of cell types and factors that work in concert across the vasculature. The vasoactive eicosanoid, 20-Hydroxyeicosatetraenoic acid (20-HETE) is a key player in this system influencing the sensitivity of the vasculature to constrictor stimuli, regulating endothelial function, and influencing the renin angiotensin system (RAS), as well as being a driver of vascular remodeling independent of blood pressure elevations. Several of these bioactions are accomplished through the ligand-receptor pairing between 20-HETE and its high-affinity receptor, GPR75. This 20-HETE axis is at the root of various vascular pathologies and processes including ischemia induced angiogenesis, arteriogenesis, septic shock, hypertension, atherosclerosis, myocardial infarction and cardiometabolic diseases including diabetes and insulin resistance. Pharmacologically, several preclinical tools have been developed to disrupt the 20-HETE axis including 20-HETE synthesis inhibitors (DDMS and HET0016), synthetic 20-HETE agonist analogues (20-5,14-HEDE and 20-5,14-HEDGE) and 20-HETE receptor blockers (AAA and 20-SOLA). Systemic or cell-specific therapeutic targeting of the 20-HETE-GPR75 axis continues to be an invaluable approach as studies examine the molecular underpinnings activated by 20-HETE under various physiological settings. In particular, the development and characterization of 20-HETE receptor blockers look to be a promising new class of compounds that can provide a considerable benefit to patients suffering from these cardiovascular pathologies.

Matched MeSH terms: Renin-Angiotensin System*
Fulltext Possible Benefits of Zinc supplement in CVD and COVID-19 Comorbidity

Karim MM, Sultana S, Sultana R, Rahman MT

J Infect Public Health, 2021 Nov;14(11):1686-1692.
PMID: 34649043 DOI: 10.1016/j.jiph.2021.09.022

As far as comorbidity is concerned, cardiovascular diseases (CVD) appear to be accounted for the highest prevalence, severity, and fatality among COVID 19 patients. A wide array of causal links connecting CVD and COVID-19 baffle the overall prognosis as well as the efficacy of the given therapeutic interventions. At the centre of this puzzle lies ACE2 that works as a receptor for the SARS-CoV-2, and functional expression of which is also needed to minimize vasoconstriction otherwise would lead to high blood pressure. Furthermore, SARS-CoV-2 infection seems to reduce the functional expression of ACE2. Given these circumstances, it might be advisable to consider a treatment plan for COVID-19 patients with CVD in an approach that would neither aggravate the vasodeleterious arm of the renin-angiotensinogen-aldosterone system (RAAS) nor compromise the vasoprotective arm of RAAS but is effective to minimize or if possible, inhibit the viral replication. Given the immune modulatory role of Zn in both CVD and COVID-19 pathogenesis, zinc supplement to the selective treatment plan for CVD and COVID-19 comorbid conditions, to be decided by the clinicians depending on the cardiovascular conditions of the patients, might greatly improve the therapeutic outcome. Notably, ACE2 is a zinc metalloenzyme and zinc is also known to inhibit viral replication.

Matched MeSH terms: Renin-Angiotensin System
Plasma renin and aldosterone in thyroid diseases

Asmah BJ, Wan Nazaimoon WM, Norazmi K, Tan TT, Khalid BA

Horm. Metab. Res., 1997 Nov;29(11):580-3.
PMID: 9479560 DOI: 10.1055/s-2007-979105

The effect of thyroid hormones on the renin-angiotensin-aldosterone system has not been fully resolved. Highly specific immunoassays for measurement of renin, aldosterone, free T4 (fT4), free T3 (fT3) and ultrasensitive TSH enables a direct and more accurate measurement of these hormones. We investigated the relationship between plasma renin, aldosterone and thyroid hormones in the basal state and after intravenous frusemide. This is a cross-sectional study involving 37 patients with thyrotoxicosis, 42 rendered euthyroid with normal fT4, fT3 and TSH levels, 17 with euthyroid levels of fT4 and fT3 but suppressed TSH, and 11 with hypothyroidism. Basal plasma renin was significantly higher in thyrotoxicosis (63.4 +/- 9.8 microU/ml, mean +/- SEM) compared to euthyroid (32.7 +/- 4.4 microU/ml) and hypothyroid (26.7 +/- 9.8 microU/ml). Basal plasma renin for euthyroid with suppressed TSH (41.0 +/- 7.4 microU/ml) was significantly higher than hypothyroid (p = 0.02). Basal plasma aldosterones were not significantly different except for suppressed TSH (157.7 +/- 13 pg/ml), which was higher than normal (109.9 +/- 10.4 pg/ml; p = 0.04). Following frusemide, plasma renin and aldosterone were significantly increased in all groups. Plasma renin was highly correlated to fT3 (r = 0.405, p < 0.001), total T3 (r = 0.359, p < 0.001), fT4 (r = 0.331, p < 0.001) and TSH (r = 0.300, p < 0.001) in the basal state, but less to total T4 (r = 0.248, p < 0.01). Plasma renin correlated poorly to serum aldosterone (r = 0.212, p < 0.03). This study clearly showed that regulation of renin was mainly influenced by fT3, and that aldosterone response to frusemide was blunted in thyrotoxicosis despite normal electrolytes.

Matched MeSH terms: Renin/blood*; Renin/drug effects
Fulltext Possible Protective Effect of Renin-Angiotensin System Inhibitors in COVID-19 Induced Acute Kidney Injury

Kow CS, Hasan SS

J Am Soc Nephrol, 2020 08;31(8):1917-1918.
PMID: 32639940 DOI: 10.1681/ASN.2020050640
Matched MeSH terms: Renin-Angiotensin System
ß-blockers in congestive heart failure

Teh BT, Wan Azman WA, Thuraisingham S, Choy AM, Tan KH, Jesudason P, et al.

JUMMEC, 1999;4:26-33.

Activation of the synlpathetic nervous system (SNS) and renin-angiotensin system (RAS) plays a pivotal role in the pathophysiology and progression of the disease in chronic heart failure (CHF). Blocking the activation of the RAS with angiotensin converting enzyme inhibitors not only improves sylnptonls but also prolongs life in symptomatic CHF. Does a similar analogy hold true for the use of ß-blockers in CHF? Evidence from a number of small trials and several recent large prospective trials show that b-blockers may improve ventricular function and symptoms in CHF. In a combination of trials investigating the use of carvedilol (an α, and ß-blocker) in congestive heart failure a mortality benefit appears to be evident. There are still a number of key questions that relnaill unanswered regarding the tolerability, patient type and stage of CHF in which ß-blockers should be advocated. Several large scale trials are in progress to answer some of these questions and also to add further information regarding its efficacy and impact on survival. KEYWORDS: Beta-adrenoreceptor antagonist, congestive heart failure.

Matched MeSH terms: Renin-Angiotensin System
Fulltext RAAS inhibitors in COVID-19: They are not all the same!

Kow CS, Ramachandram DS, Hasan SS

Rev Port Cardiol, 2023 Sep;42(9):815-816.
PMID: 37353197 DOI: 10.1016/j.repc.2023.04.008
Matched MeSH terms: Renin-Angiotensin System
Fulltext The improvement of hypertension by probiotics: effects on cholesterol, diabetes, renin, and phytoestrogens

Lye HS, Kuan CY, Ewe JA, Fung WY, Liong MT

Int J Mol Sci, 2009 Sep;10(9):3755-75.
PMID: 19865517 DOI: 10.3390/ijms10093755

Probiotics are live organisms that are primarily used to improve gastrointestinal disorders such as diarrhea, irritable bowel syndrome, constipation, lactose intolerance, and to inhibit the excessive proliferation of pathogenic intestinal bacteria. However, recent studies have suggested that probiotics could have beneficial effects beyond gastrointestinal health, as they were found to improve certain metabolic disorders such as hypertension. Hypertension is caused by various factors and the predominant causes include an increase in cholesterol levels, incidence of diabetes, inconsistent modulation of renin and imbalanced sexual hormones. This review discusses the antihypertensive roles of probiotics via the improvement and/or treatment of lipid profiles, modulation of insulin resistance and sensitivity, the modulation of renin levels and also the conversion of bioactive phytoestrogens as an alternative replacement of sexual hormones such as estrogen and progesterone.

Matched MeSH terms: Renin/metabolism*
Fulltext The blood pressure variability, arterial elasticity and humoral factors in subjects with family history of hypertension

Rafidah HM, Azizi A, Suhaimi H, Noriah MN

Med J Malaysia, 2008 Mar;63(1):9-16.
PMID: 18935724 MyJurnal

Normotensive subjects with family history of hypertension (FHT) have been reported to have increased left ventricular mass index and reduced ventricular compliance. Of interest is whether blood pressure variability (BPV), which has been associated with target organ damage, is then part of this complex inherited syndrome? The objectives of this study are to determine whether there are any significant differences in BPV, arterial compliance and humoral factors in subjects with FHT as compared to controls. Thirty-five subjects with self reported FHT and 35 matched controls underwent 24 hour BP monitoring (BR-102, Schiller Inc. Germany). Arterial compliance was measured using systolic pulse wave tonometry (HDI/Pulsewave Cardiovascular Profiling Instrument, Hypertension Diagnostic Inc. USA). None of the subjects were hypertensive or diabetic. Out of these numbers, 25 subjects with FHT and 26 controls had measurements of plasma catecholamines, plasma renin and serum aldosterone. Catecholamines were assayed with high performance liquid chromatography, while both renin and aldosterone measurements were by radioimmunoassay. Subjects with FHT have higher night time BPV. There was no significant difference in arterial compliances between both groups. There were increased level of norepinephrine (NE) in subjects with FHT but epinephrine (E), renin and aldosterone levels were similar in both groups. There were no correlations between NE and BPV but E was negatively associated with daytime and mean arterial systolic BPV. In conclusion subjects with FHT demonstrated a higher night time BPV and NE level as compared to controls.

Matched MeSH terms: Renin/blood*
Fulltext Functioning adrenal adenoma in association with congenital adrenal hyperplasia

Rohana AG, Ming W, Norlela S, Norazmi MK

Med J Malaysia, 2007 Jun;62(2):158-9.
PMID: 18705452 MyJurnal

We report a case of a young hypertensive male who was first seen in 1998 with a right thalamic haemorrhage and uncontrolled hypertension. CT abdomen showed a right adrenal tumour and a hyperplastic left adrenal gland. Laparoscopic adrenalectomy performed followed by histopathological examination confirmed the diagnosis of adrenal adenoma. He subsequently presented to us again a year later with persistent hyperkalaemia and asymptomatic hyponatraemia. Further investigations strongly suggested the presence of isolated mineralocorticoid deficiency with normal cortisol levels. This was confirmed to be due to partial or late-onset congenital adrenal hyperplasia (CAH). We discuss the association of partial CAH and adrenal tumours and the unmasking of the mineralocorticoid deficiency following adrenalectomy.

Matched MeSH terms: Renin/blood
Fulltext Serum and urinary divalent cations and plasma renin activity in women with mild pregnancy-induced hypertension

Singh HJ

Med J Malaysia, 1995 Mar;50(1):93-100.
PMID: 7752984

Serum concentrations and urinary output of calcium, magnesium, sodium and potassium were analysed in normotensive pregnant women and in women with pregnancy-induced hypertension during the third trimester. In addition, plasma renin activity (PRA) was also determined. Significantly lower serum total calcium, urinary calcium and magnesium excretions and plasma renin activity were evident in women with PIH. Urine output and creatinine clearance were not significantly different between the two groups. No significant correlation was evident between serum calcium, magnesium and PRA. The relationship between these parameters and high blood pressure is not immediately apparent. They nevertheless suggest of a disturbance in electrolyte metabolism in women with PIH, that may underly the pathogenesis of this disorder.

Matched MeSH terms: Renin/blood*
Reference values of hematological, serum biochemical and hormonal examinations in female cynomolgus monkeys (Macaca fascicularis) of feral origin

Yoshida T, Katsuta A, Cho F

Jikken Dobutsu, 1989 Jul;38(3):259-62.
PMID: 2676567

Blood samples were collected from clinically healthy female cynomolgus monkeys imported from Indonesia, the Philippines and Malaysia. These animals were maintained under uniform environmental conditions for four to five years. The blood samples were examined for their hematological, serum biochemical and hormonal values. The ranges of the values as well as their arithmetic means and standard deviations have been tabulated with respect to each examination item.

Matched MeSH terms: Renin/blood

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