Aldosteronism Hypertension Research Articles

Systematic review/meta-analysis and a cross-sectional study to assess effects of potassium supplementation on the renin-angiotensin-aldosterone system (RAAS) and blood pressure

Abstract Introduction Nutritional medicine plays a key role in disease prevention and treatment, and we pharmacists must consider our contribution beyond our role in dispensing. Apart from the Dietary Approaches to Stop Hypertension (DASH) diet1, there is a paucity of data on the benefits of nutritional interventions in hypertension with no clear recommendation on potassium in the NICE guidelines. Potassium has been an area of interest in clinical medicine over the decades because of its effect on cardiovascular disease. However, its mechanism of action is poorly understood, and it is unclear it differs between different ethnic groups. Dietary potassium decreases blood pressure (BP) but can also stimulate aldosterone production2. However, the magnitude of potassium-dependent regulation of aldosterone secretion in humans is not fully characterised and it is not clear whether this is mediated by activation of the renin-angiotensin-aldosterone system (RAAS) as a result of a reduction in BP or other mechanisms. Aim To perform a (1) systematic review and meta-analysis of clinical trials assessing effects of potassium on plasma aldosterone and renin in adult individuals alongside a (2) cross-sectional multi-ethnic study to explore the relationship between potassium intake and aldosterone in hypertension. Methods (1) This study was carried out in accordance with PRISMA guidelines3. The full protocol can be found on the PROSPERO database. (2) Self-defined black or white hypertensives were recruited from the hypertension outpatient clinic at St. Thomas’ Hospital and had aldosterone, renin and a 24-hour urinary potassium collected. The systematic review and meta-analysis on already approved clinical trials and did not require ethnical approval. The cross-sectional study was approved by the local Research Ethics Committee in the UK and written informed consent was obtained from all patients. Results 6395 articles were retrieved, and 124 full-text articles were assessed for eligibility. 36 met the prespecified inclusion/exclusion criteria. Potassium supplementation caused a significant decrease in systolic BP (- 3.69 mmHg [-4.91, -2.46], P<0.001) and increase in serum potassium (+0.37 [0.23, 0.52] mmol/L, P<0.001). There was an increase in plasma aldosterone (standardised difference 0.414 [0.291, 0.537], P<0.001) but no effect on plasma renin activity (+0.033 [-0.07, 0.14], P=0.538]. Meta-regression showed a significant positive correlation between change in plasma aldosterone and change in serum potassium (P<0.001). (2) In 469 subjects (72% black), there was a positive association between the measured 24-hour potassium excretion and aldosterone in black (β = 0.200, P = 0.014) but not in white individuals (P = 0.531). Discussion/Conclusion Potassium supplementation increases plasma aldosterone but not renin. The increase in aldosterone correlates with the raise in serum potassium. In subjects with hypertension, potassium intake is related with aldosterone concentration only in black subjects. Overall, the data supports a RAAS-independent potassium regulation of aldosterone which could be particularly relevant in African origin subjects. Limitations: 1. the systematic review results could not be stratified by ethnicity because most of the studies were performed in Caucasian subjects, 2. Use of background therapy in some studies, variable doses of potassium supplementation and duration of supplementation.

MANP (M-Atrial Natriuretic Peptide) Reduces Blood Pressure and Furosemide-Induced Increase in Aldosterone in Hypertension.

cGMP MANP (M-atrial natriuretic peptide) is a best-in-class activator of the pGC-A (particulate guanylyl cyclase A) receptor. Furosemide increases the effectiveness of antihypertensive agents, but activates renin-angiotensin-aldosterone system. We aimed to investigate for the first time cardiorenal and neurohumoral actions of MANP in a genetic model of hypertension in spontaneously hypertensive rats. We also assessed how MANP would potentiate the blood pressure (BP)-lowering actions of furosemide while reducing the production of aldosterone. Spontaneously hypertensive rats (N=60) were randomized in vehicle, MANP, furosemide, or MANP+furosemide groups. Furosemide (1, 5, 10 mg/kg) was given as a single bolus which in MANP+furosemide groups was followed by a 60-minute infusion of MANP. BP was reduced in MANP300 (300 pmol/[kg·min]) and MANP600 (600 pmol/[kg·min]) groups (P<0.05) and was accompanied by significant increase in plasma cyclic guanosine monophosphate. Furosemide alone reduced BP but less compared with MANP with no change in plasma cyclic guanosine monophosphate. MANP+furosemide resulted in the greatest BP reduction and significant increase in plasma cyclic guanosine monophosphate in Fs5+MANP300, Fs10+MANP300, and Fs10+MANP600. Plasma aldosterone increased in furosemide groups, which was significantly attenuated in MANP+furosemide groups. Natriuresis and diuresis increased in all treated groups (P<0.05) with no significant differences between furosemide and furosemide+MANP. In vitro, MANP increased cyclic guanosine monophosphate level in human vascular cells. We provide novel evidence that MANP potentiates the BP-lowering actions of furosemide, suppresses the activation of renin-angiotensin-aldosterone system, and preserves renal function. These data are highly relevant to clinical needs in the treatment of hypertension and heart failure.

Modulation of 11β-hydroxysteroid dehydrogenase functions by the cloud of endogenous metabolites in a local microenvironment: The glycyrrhetinic acid-like factor (GALF) hypothesis

11β-Hydroxysteroid dehydrogenase (11β-HSD)-dependent conversion of cortisol to cortisone and corticosterone to 11-dehydrocorticosterone are essential in regulating transcriptional activities of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR). Inhibition of 11β-HSD by glycyrrhetinic acid metabolites, bioactive components of licorice, causes sodium retention and potassium loss, with hypertension characterized by low renin and aldosterone. Essential hypertension is a major disease, mostly with unknown underlying mechanisms. Here, we discuss a putative mechanism for essential hypertension, the concept that endogenous steroidal compounds acting as glycyrrhetinic acid-like factors (GALFs) inhibit 11β-HSD dehydrogenase, and allow for glucocorticoid-induced MR and GR activation with resulting hypertension. Initially, several metabolites of adrenally produced glucocorticoids and mineralocorticoids were shown to be potent 11β-HSD inhibitors. Such GALFs include modifications in the A-ring and/or at positions 3, 7 and 21 of the steroid backbone. These metabolites may be formed in peripheral tissues or by gut microbiota. More recently, metabolites of 11β-hydroxy-Δ4androstene-3,17-dione and 7-oxygenated oxysterols have been identified as potent 11β-HSD inhibitors. In a living system, 11β-HSD isoforms are not exposed to a single substrate but to several substrates, cofactors, and various inhibitors simultaneously, all at different concentrations depending on physical state, tissue and cell type. We propose that this “cloud” of steroids and steroid-like substances in the microenvironment determines the 11β-HSD-dependent control of MR and GR activity. A dysregulated composition of this cloud of metabolites in the respective microenvironment needs to be taken into account when investigating disease mechanisms, for forms of low renin, low aldosterone hypertension.

A HIGH ALDOSTERONE TO RENIN RATIO MEDIATES MICROVASCULAR AND MACROVASCULAR DAMAGE IN NEWLY-DIAGNOSED, TREATMENT-NAÏVE ESSENTIAL HYPERTENSION

Objective: The role of aldosterone in hypertension was generally considered in the context of primary hyperaldosteronism, an uncommon condition (less than 2% in the hypertensive population). However, based on an increased ambulant aldosterone-to-renin ratio (ARR), a marker of inappropriate aldosterone activity, the prevalence of primary hyperaldosteronism in the hypertensive population may be as high as 10% to 15%. There is increasing evidence to suggest a BP-independent effect of aldosterone on left ventricular structure, increased collagen deposition with fibrosis, diastolic dysfunction and arterial stiffness. We hypothesized that aldosterone and renin will be associated with microvascular and macrovascular alterations in never treated essential hypertension. Design and method: We prospectively studied newly diagnosed, untreated essential hypertensive and normotensive subjects (n = 1482, 47% females, mean age 51 ± 0.77, SEM). Pulse wave velocity (PWV), augmentation index (AIx), aortic systolic BP and pulse pressure amplification were measured with applanation tonometry(SphygmoCor). Albumin-creatinine ratio, urine sodium and potassium concentrations were determined from spot urine samples. Laboratory tests included serum creatinine and clearance, plasma renin activity, serum aldosterone, and high-sensitivity C-reactive protein(hs-CRP). Aldosterone to renin ratio(ARR) was divided into tertiles. Results were analysed using JMP Pro(Version 13, SAS for Windows). The patients gave informed consent and the study had Institutional ethics committee permission. Results: The top ARR tertile was associated with the highest levels of brachial BP, aortic systolic BP, AIx, pulse pressure amplification and PWV(P &lt; 0.001 for all). Stepwise regression analysis showed that the positive association between PWV and increasing ARR tertiles remained significant after adjustment for BP, age and other potential confounders(R2 = 0.39, p &lt; 0.05). The top ARR tertile was also associated with high potassium and low sodium urinary excretion, high ACR, low creatinine clearance and high hs-CRP (All p &lt; 0.01). Conclusions: In untreated hypertensive subjects with mild to moderate hypertension, there are significant interactions between ARR and indices of microvascular and macrovascular damage. Our findings indicate that aldosterone and renin adversely modulate microvascular and macrovascular function very early in the evolution of hypertension. While aldosterone antagonism is recommended currently for treatment-resistant hypertension, our findings suggest that it should be initiated early in hypertension.

Characteristics of abdominal fat distribution in patients with primary aldosteronism

Objective To compare the abdominal fat distribution in patients with primary aldosteronism (PA) and essential hypertension (EH), and to analyze the correlation between abdominal fat area and indexes such as glycolipid metabolism and insulin resistance. Methods Forty-five PA and 55 EH patients were collected from inpatients in the First Affiliated Hospital of Zhengzhou University for suspicious secondary hypertension, from September 2016 to February 2019. All patients received quantitative computed tomography to measure the total abdominal fat area (TFA), visceral fat area (VFA), and subcutaneous fat area (SFA) when receiving adrenal CT detection. Visceral obesity was defined as VFA≥130 cm2. The percentage of visceral fat area in total abdominal fat area (V%=VFA/TFA), the ratio of visceral fat area to subcutaneous fat area (V/S=VFA/SFA) and the percentage of visceral obesity were calculated. Results TFA and VFA in EH group were higher than those in PA group matched by age, gender, and body mass index (BMI, all P<0.01), and there were no statistically significant differences in SFA, V%, V/S, and the percentage of visceral obesity between the two groups. In PA group, TFA and VFA were positively correlated with homeostasis model assessment of insulin resistance index (P<0.01), TFA was positively correlated with triglycerides (TG) and low density lipoprotein-cholesterol, while SFA was positively correlated with TG (all P<0.05). Conclusion Compared with EH patients matched by age, gender, and BMI, TFA and VFA in PA patients are lower. Abdominal fat area is associated with insulin resistance and blood lipids in PA patients, while VFA exerts a greater effect on insulin resistance than that of TFA and SFA. Key words: Primary aldosteronism; Abdominal fat area; Insulin resistance; Quantitative computed tomography

Targeted disruption of the Kcnj5 gene in the female mouse lowers aldosterone levels.

Aldosterone is released from adrenal zona glomerulosa (ZG) cells and plays an important role in Na and K homoeostasis. Mutations in the human inwardly rectifying K channel CNJ type (KCNJ) 5 (KCNJ5) gene encoding the G-coupled inwardly rectifying K channel 4 (GIRK4) cause abnormal aldosterone secretion and hypertension. To better understand the role of wild-type (WT) GIRK4 in regulating aldosterone release, we have looked at aldosterone secretion in a Kcnj5 knockout (KO) mouse. We found that female but not male KO mice have reduced aldosterone levels compared with WT female controls, but higher levels of aldosterone after angiotensin II (Ang-II) stimulation. These differences could not be explained by sex differences in aldosterone synthase (Cyp11B2) gene expression in the mouse adrenal. Using RNAseq analysis to compare WT and KO adrenals, we showed that females also have a much larger set of differentially expressed adrenal genes than males (395 compared with 7). Ingenuity Pathway Analysis (IPA) of this gene set suggested that peroxisome proliferator activated receptor (PPAR) nuclear receptors regulated aldosterone production and altered signalling in the female KO mouse, which could explain the reduced aldosterone secretion. We tested this hypothesis in H295R adrenal cells and showed that the selective PPARα agonist fenofibrate can stimulate aldosterone production and induce Cyp11b2. Dosing mice in vivo produced similar results. Together our data show that Kcnj5 is important for baseline aldosterone secretion, but its importance is sex-limited at least in the mouse. It also highlights a novel regulatory pathway for aldosterone secretion through PPARα that may have translational potential in human hyperaldosteronism.

Application of endothelial markers detection in early target organ damage degree determination for patients with primary aldosteronism

Objective To compare plasma concentrations of biomarkers of endothelial dysfunction between patients with primary aldosteronism （PA） and essential hypertension （EH）,and to determine whether elevated levels of these biomarkers could predict development of early organ damage .Methods 56 PA patients （ the observation group） and 56 EH patients（the control group） matched for age,sex,blood pressure and duration of hypertension were included in this study .The plasma levels of biomarkers reflecting endothelial dysfunction [ von Willebrand factor （vWF）,soluble intercellular adhesion molecule 1（sICAM-1）,oxidized low density lipoprotein（ox-LDL）]were detec-ted and compared between PA and EH patients .The left ventricular mass index （ LVMI） determined by echocardio-graphy,24-hour urinary protein quantitative determination and urinary albumin excretion rate （ UAER） were analyzed to evaluate early organ damage .Results （ 1 ） In the observation group , the plasma markers of endothelial damage vWF （133.4 ±54.9）%,sICAM-1 （412.1 ±75.2）μg/L and ox-LDL （13.7 ±9.0） U/L levels were higher than those in the control group（t=4.642,3.955,2.843,all P〈0.05）,and the observation group had a higher 24 h urina-ry protein（t=2.042,P〈0.05） and LVMI（t=7.235,P〈0.05）.（2）Correlation analysis showed that LVMI was positively correlated with PAC,ox-LDL,vWF （r=0.447,0.385,0.393,P=0.020,0.046,0.029）,and was nega-tively correlated with admission blood K ＋（r=-0.294,P〈0.05）.UAER was positively correlated with PAC,vWF and sICAM-1 （r=0.622,0.389,0.499,all P〈0.05）,and was negatively correlated with admission blood K ＋（r=-0.314,P〈0.05）.Conclusion Patients with PA have severer endothelial dysfunction reflected by multiple bio-markers and earlier organ damage than patients with EH ,and plasma aldosterone concentration and multiple endotheli-al dysfunction biomarkers could independently predict early organ damage . Key words: Hyperaldosteronism; Endothelium,vascular; Biological markers

Sleep Disordered Breathing as an Independent Predictor of Post-Discharge Mortality in Patients with Acutely Decompensated Heart Failure

Introduction: Aldosterone promotes sodium and water retention and mediates inflammation and fibrosis. Aldosterone may be inappropriately high in hypertensive patients and recent studies have established that it may be higher in obese subjects and in the metabolic syndrome (MetS), although within the normal range. To date, aldosterone concentrations in the general population and the relationship to co-morbidities as well as metabolic and cardiorenal parameters have not been well defined. Hypothesis: We hypothesized that aldosterone levels correlate with the prevalence of cardiorenal and metabolic diseases in a general community including metabolic parameters and cardiac structure.Methods:We evaluated the association between aldosterone levels, cardiometabolic parameters and cardiorenal disease in a general community-based cohort from Olmsted County, MN (1674 subjects 45 years and older). We also assessed cardiac structure and function by echocardiography. Results: Median level of aldosterone was 4.6 ng/dl (Q1 2.50, Q3 8.00 ng/dl). Multivariate analysis adjusted for age, gender, BMI and ANP showed a significant correlation between aldosterone levels and hypertension (p!0.0001, OR52.28, CI:1.91-2.71), atrial fibrillation (p!0.01, OR51.53, CI:1.11-2.11), chronic kidney disease (CKD) (p!0.0001, OR51.64, CI:1.33-2.02), central obesity (p!0.0001, OR51.61, CI:1.27-2.05), hypertriglyceridemia (p!0.003, OR51.27, CI:1.08-1.48), prevalence of MetS (p!0.0007, OR51.40, CI51.15-1.71) and obesity (p!0.0001, OR51.48, CI:1.27-1.73). These associations remained significant even after including BNP levels in the multivariate regression models. Aldosterone levels were also associated with concentric hypertrophy and preserved left ventricular ejection fraction. Conclusions: In a general community-based cohort from Olmsted County MN, aldosterone is powerfully associated with cardiovascular, renal and metabolic diseases including alterations in cardiac structure. Specifically, aldosterone was strongly associated with hypertension, CKD, atrial fibrillation, obesity, MetS per se as well as its individual components. This study strongly supports aldosterone as a marker for human cardiorenal and metabolic diseases and/or as a potential mediator of these diseases even in the general adult population prior to over disease. Further studies are warranted to evaluate possible therapeutic interventions targeting aldosterone as a strategy to delay disease progression.

Is there truly a sympathetic component to aldosterone hypertension?

Studies in rodents suggest that sympathetic activation may contribute to aldosterone (Aldo) hypertension (HT), but evidence in non‐rodent animals and in humans is equivocal. The goal of this study was to use complementary techniques to determine whether sympathetic activation contributes to HT induced by high circulating levels of Aldo. After control measurements, Aldo was infused IV for 14 days at 12μg/kg/day in 9 dogs maintained on a constant Na intake (~65 mmol/day). This increased plasma Aldo (control= 4.3±0.4 ng/dL) ~ 10‐fold and mean arterial pressure (MAP) from 103±2 to 121±5 mmHg. In addition, Aldo infusion was associated with marked polydipsea, increases in plasma osmolality (293±1 to 297±1 mOsm/kg H20) and vasopressin (0.86±.32 to 1.73±0.34 pg/mL), hypokalemia (4.2±0.1 to 2.3±0.1) and suppression of PRA to undetectable levels. Despite these responses, there were no significant changes in plasma [norepinephrine], and depressor responses to ganglionic blockade with hexamethonium (5 mg, IV) were actually attenuated during Aldo HT, suggesting suppression of sympathetic activity. Finally, in 2 dogs, bilateral renal denervation failed to attenuate Aldo HT. In these dogs, MAP was 122 and 142 before and 122 and 144 two weeks after bilateral renal denervation. Thus, the failure of both global and renal specific measures to demonstrate sympathetic activation indicates that classic renal mineralocorticoid mechanisms account for the initial progression of HT produced by pathophysiological circulating levels of Aldo. HL‐51971

WITHDRAWN: Association between the levels of carboxy-terminal propeptide of type I procollagen and aldosterone in patients with primary aldosteronism and essential hypertension

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Primary aldosteronism and resistant arterial hypertension

The review discusses the new data about primary aldosteronism and the connection between increase of aldosterone level and resistance to antihypertensive treatment, including patients with obstructive sleep apnea. Also the main pathophysiological mechanisms underlying the progression of end organ damage and leading to resistance to antihypertensive treatment in patients with high aldosterone level are presented.

Overlapping Spironolactone Dosing in Primary Aldosteronism and Resistant Essential Hypertension

Overlapping Spironolactone Dosing in Primary Aldosteronism and Resistant Essential Hypertension

Primary Aldosteronism and Public Health: New Definitions, New Challenges

The article, “Primary Aldosteronism: Are We Missing the Wood for the Trees?” <xref idref="R2012-05-0157-0001">1</xref>, to which Piaditis et al. refer <xref idref="R2012-05-0157-0002">2</xref>, makes a series of 5 points. The first is that on the current estimates on the prevalence of hypertension, and of primary aldosteronism in hypertension, in no country worldwide are more than 1% of patients with primary aldosteronism diagnosed and treated. The second is that to diagnose primary aldosteronism in the remaining >99% of patients, and then appropriately manage them, is way beyond the available health care resources in any country. The third is that primary aldosteronism has a risk profile, in terms of atrial fibrillation, stroke, and nonfatal myocardial infarct, far higher than age-, sex-, and blood pressure-matched essential hypertension <xref idref="R2012-05-0157-0003">3</xref>. The fourth is that mineralocortoid receptor antagonism is safe, efficacious, and uniquely vasoprotective in essential hypertension when titrated to effect <xref idref="R2012-05-0157-0004">4</xref> <xref idref="R2012-05-0157-0005">5</xref>, specifically blood pressure lowering in resistant hypertension <xref idref="R2012-05-0157-0006">6</xref>, and potentially game-changing in occult primary aldosteronism. The final point is the logical conclusion drawn from the first four – that a low dose mineralocortoid receptor antagonist should routinely be part of first line therapy in newly diagnosed hypertensives.

Left Heart Morphology and Function in Primary Aldosteronism

Primary aldosteronism is the most frequent cause of secondary hypertension, accounting for up to 11% of cases in selected populations. Patients affected by primary aldosteronism have shown higher prevalence of cardiovascular and cerebrovascular events compared with patients with essential hypertension, despite similar blood pressure levels. Several studies have been performed over past years aiming to explain these data; many of these evaluated echocardiographic differences in hypertension-related cardiac organ damage between primary aldosteronism and essential hypertension. This article summarizes the present knowledge about structural and functional alteration of the human left heart in primary aldosteronism.

A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism

A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism

A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism

Eplerenone is claimed to be a more selective blocker of the mineralocorticoid receptor than spironolactone being associated with fewer antiandrogenic side-effects. We compared the efficacy, safety and tolerability of eplerenone versus spironolactone in patients with hypertension associated with primary aldosteronism. The study was multicentre, randomized, double-blind, active-controlled, and parallel group design. Following a single-blind, placebo run-in period, patients were randomized 1: 1 to a 16-week double-blind, treatment period of spironolactone (75-225 mg once daily) or eplerenone (100-300 mg once daily) using a titration-to-effect design. To be randomized, patients had to meet biochemical criteria for primary aldosteronism and have a seated DBP at least 90 mmHg and less than 120 mmHg and SBP less than 200 mmHg. The primary efficacy endpoint was the antihypertensive effect of eplerenone versus spironolactone to establish noninferiority of eplerenone in the mean change from baseline in seated DBP. Changes from baseline in DBP were less on eplerenone (-5.6 ± 1.3 SE mmHg) than spironolactone (-12.5 ± 1.3 SE mmHg) [difference, -6.9 mmHg (-10.6, -3.3); P<0.001]. Although there were no significant differences between eplerenone and spironolactone in the overall incidence of adverse events, more patients randomized to spironolactone developed male gynaecomastia (21.2 versus 4.5%; P=0.033) and female mastodynia (21.1 versus 0.0%; P=0.026). The antihypertensive effect of spironolactone was significantly greater than that of eplerenone in hypertension associated with primary aldosteronism.

Outpatient Evaluation of Secondary Causes of Resistant Hypertension

Primary aldosteronism, pheochromocytoma and renovascular hypertension are hypertensive syndromes often associated with resistant hypertension. Early recognition of these disorders has come as the result of a better understanding of their pathophysiology. Prompt and definitive diagnosis has resulted from the availability of sensitive and accurate diagnostic tools. Finally, safe and effective pharmacotherapeutic agents and innovative surgical techniques have led to excellent and predictable clinical outcomes.

Renin-Angiotensin Aldosterone System and Hypertension: Current Approaches and Future Directions

Renin-Angiotensin Aldosterone System and Hypertension: Current Approaches and Future Directions

Interaction between the heme oxygenase system and aldosterone in hypertension

The chronic intraperitoneal administration of the heme oxygenase inducer, hemin (15 mg/kg daily), for three weeks reduced blood pressure in adult spontaneously hypertensive rats (SHR) from 210.1±1.03 mmHg to 127±0.9 mmHg (n=10, P<0.01) but had no effect on age-matched normotensive Wistar-Kyoto or Sprague-Dawley strains. The antihypertensive effect of hemin was accompanied by reduced expression of aldosterone synthase messenger RNA and depleted levels of plasma aldosterone (675.7±121.6 pg/mL versus 365.7±37 pg/mL; n=4, P<0.05).Because aldosterone is known to stimulate phospholipase C (PLC), the effect of hemin on PLC was examined. Hemin abated PLC activity (29.6±1.5 nmol/min/mL versus 3.1±0.9 nmol/min/mL; n=5, P<0.01) and this was accompanied by depleted levels of intracellular calcium (551±46 nM versus 103.2±6.3 nM; n=4, P<0.01) in the aorta of SHR. In contrast, enhanced heme oxygenase activity and elevated cyclic GMP levels (17.74±0.08 pmol/mg versus 30.4±2.3 pmol/mg protein; n=6, P<0.01) were detected in hemin-treated SHR. Additionally, hemin therapy also suppressed inflammatory and oxidative insults by significantly reducing nuclear factor kappa B messenger RNA expression while enhancing the total antioxidant capacity (0.22±0.02 Trolox equivalent antioxidant capacity (TEA C)/mg protein versus 0.60±0.04 TEA C/mg protein; n=4, P<0.01).The concomitant depletion of aldosterone, PLC activity, intracellular calcium and the corresponding decline of inflammatory and oxidative insults may account for the antihypertensive effects of hemin.

Comparison of Target Organ Damages between Primary Aldosteronism and Essential Hypertension

Background: A number of recent clinical studies have reported marked target organ damages in patients with primary aldosteronism. The aim of this study was to compare the incidence of target organ damages in patients with primary aldosteronism (PA) and essential hypertension (EHT). Methods: The clinical records of 41 PA patients, over a 20-year period, were retrospectively analyzed. The clinical characteristics and incidence of target organ damages of 33 of the patients in this group were compared with those of 66 patients with essential hypertension, directly matched for age, gender and mean blood pressure. 8 of the PA patients could not be matched with EHT patients for age, gender and mean blood pressure, so were excluded from the comparison. The patients with essential hypertension were sampled from patients who visited for the evaluation of hypertension. Results: Ischemic heart diseases were found in 18.2 and 10.6% of patients with PA and EHT, respectively (P = 0.22). From echocardiograms, left ventricular hypertrophy was found in 93.3% and 61.4% of patients with PA and EHT, respectively (P = 0.017). The degrees of left ventricular hypertrophy were correlated with the levels of serum aldosterone, with an r value of 0.490 (P < 0.005). Cerebrovascular attack was found in 18.2% and 1.5% of patients with PA and EHT, respectively (P = 0.005). Hypertensive retinopathy was found in 50% and 33.3% of patients with PA and EHT (P = 0.255), and nephropathy was found in 42.4% and 25.8% of patients with PA and EHT, respectively (P = 0.074). Conclusion: Patients with primary aldosteronism had target organ damages more frequently than with those with essential hypertension, which was independent of blood pressure. (J Kor Endocrinol Soc 22:11~18, 2007)