Increase In Plasma Renin Activity Research Articles

Commensal microbiota regulate aldosterone.

The gut microbiome regulates many important host physiological processes associated with cardiovascular health and disease; however, the impact of the gut microbiome on aldosterone is unclear. Investigating whether gut microbiota regulate aldosterone can offer novel insights into how the microbiome affects blood pressure. In this study, we aimed to determine whether gut microbiota regulate host aldosterone. We used enzyme-linked immunosorbent assays (ELISAs) to assess plasma aldosterone and plasma renin activity (PRA) in female and male mice in which gut microbiota are intact, suppressed, or absent. In addition, we examined urinary aldosterone. Our findings demonstrated that when the gut microbiota is suppressed following antibiotic treatment, there is an increase in plasma and urinary aldosterone in both female and male mice. In contrast, an increase in PRA is seen only in males. We also found that when gut microbiota are absent (germ-free mice), plasma aldosterone is significantly increased compared with conventional animals (in both females and males), but PRA is not. Understanding how gut microbiota influence aldosterone levels could provide valuable insights into the development and treatment of hypertension and/or primary aldosteronism. This knowledge may open new avenues for therapeutic interventions, such as probiotics or dietary modifications to help regulate blood pressure via microbiota-based changes to aldosterone.NEW & NOTEWORTHY We explore the role of the gut microbiome in regulating aldosterone, a hormone closely linked to blood pressure and cardiovascular disease. Despite the recognized importance of the gut microbiome in host physiology, the relationship with circulating aldosterone remains largely unexplored. We demonstrate that suppression of gut microbiota leads to increased levels of plasma and urinary aldosterone. These findings underscore the potential of the gut microbiota to influence aldosterone regulation, suggesting new possibilities for treating hypertension.

Effects of potassium supplementation on plasma aldosterone: a systematic review and meta-analysis in humans.

Effects of potassium supplementation on blood pressure (BP) may be offset by an increase in plasma aldosterone. The magnitude of potassium-dependent regulation of aldosterone secretion in humans is not fully characterized; 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. We performed a systematic review and meta-analysis of clinical trials assessing effects of potassium on plasma aldosterone and renin in adult individuals. This was carried out in accordance with PRISMA guidelines. Three databases were searched: MEDLINE, EMBASE and CENTRAL. Titles were firstly screened by title and abstract for relevance before full-text articles were assessed for eligibility. The keywords used included "aldosterone", "potassium" and "RAAS". 6395 articles were retrieved and after title/abstract screening, 123 full-text articles were assessed for eligibility. Thirty-six met the prespecified inclusion/exclusion criteria (of which 18/36 also reported systolic BP). Potassium supplementation caused a significant decrease in systolic BP (mean difference [95% CI] -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 (standardized difference 0.426 [0.299, 0.553], P < 0.001) but not in plasma renin activity. Meta-regression showed a significant positive correlation between change in plasma aldosterone and change in serum potassium (P < 0.001). Potassium supplementation increases plasma aldosterone concentrations, which correlates with the increase in serum potassium concentration which does not appear to be mediated by an increase in plasma renin activity.

Solution is not simple; sodium-glucose cotransporter-2 inhibitor use in Conn syndrome.

In patients with bilateral primary hyperaldosteronism (PA) and those with unilateral PA who are unwilling or unable to undergo adrenalectomy an increase in plasma renin activity (PRA) provided by mineralocorticoid receptor antagonists (MRAs) therapy reflects sufficient antagonism for elevated aldosterone. Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) have cardiovascular, renal protective properties and some clinical data have shown an increase in PRA levels with SGLT2-i. Here, we present our experience of using SGLT2-i in PA patients with suppressed PRA despite 100 mg/day spironolactone therapy. We prospectively evaluate the laboratory values of seven patients who were diagnosed with bilateral hyperaldosteronism. All of them were diabetic and had an HbA1c <7% with metformin treatment alone. Spironolactone was started in all of the patients after diagnosis and although the dose was increased to 100 mg/day, PRA levels remained <1 ng/ml/h. Metformin treatment was changed to empagliflozin in all patients and PRA was checked again at the sixth month of treatment. Metformin treatment was changed to empagliflozin in all patients and PRA was checked again at the sixth month of treatment. Mean PRA levels were 0.464 ± 0.189 ng/ml/h before the treatment change and increased to mean 3.257 ± 1.881 ng/ml/h in the sixth month (P = 0.008). The mean PRA was >1 ng/ml/h except for one patient in the sixth month of treatment. Larger molecular and clinical studies are needed to understand whether the increase in PRA after empagliflozin treatment indicates interference, whether spironolactone treatment has become more effective, or whether empagliflozin has aldosterone receptor antagonism apart from its known effects.

META-ANALYSIS OF DEPENDENCE OF THE DEVELOPMENT OF EXPERIMENTAL RENOVASCULAR HYPERTENSION “2 KIDNEYS, 1 CLAMP” ON LIFESTYLE FACTORS

Background. According to WHO controllable hypertension risk factors include an unhealthy diet, physical inactivity, and wrong daily routine. To date, a large number of experimental studies in rats have studied the effect on the development of unilateral renovascular hypertension (URH) of dietary supplements (minerals, vitamins, flavonoids, caffeine, fats, carbohydrates), physical activity and melatonin therapy.Objective. To conduct a meta- analysis of studies on risk factors for the development of URH.Design and methods. The search for publications was carried out in the PubMed, Scopus, Google Scholar databases. A total of 52 publications were selected.Results. The severity of hypertension decreases when the diet is enriched with potassium, as well as with various antioxidants (vitamin C, flavonoids, melatonin), which reduce oxidative stress in the ischemic kidney. In addition, physical activity can help reduce blood pressure in URH, but at the same time, it increases myocardial hypertrophy. There was no hypertensive effect of increased sodium chloride intake in renal artery stenosis, and no effect of calcium or magnesium supplementation on the URH development. At the same time, caffeine intake significantly increases plasma renin activity and blood pressure in URH.Conclusion. The majority of experimental studies included in our meta-analysis investigated the influence of factors on the development of URH, but not their effect on blood pressure in the chronic stage of URH.

Plasma Renin Activity Increases With Cardiopulmonary Bypass and is Associated With Vasoplegia After Cardiac Surgery

To describe the trend in plasma renin activity over time in patients undergoing cardiac surgery on cardiopulmonary bypass, and to investigate if increased plasma renin activity is associated with postcardiopulmonary bypass vasoplegia. A prospective cohort study. Patients were enrolled from June 2020 to May 2021 at a tertiary cardiac surgical institution. A cohort of 100 adult patients undergoing cardiac surgery on cardiopulmonary bypass. None. Plasma renin activity was measured at 5 time points: baseline, postoperatively, and at midnight on postoperative days 1, 2, and 3. Plasma renin activity and delta plasma renin activity were correlated with the incidence of vasoplegia and clinical outcomes. The median plasma renin activity increased approximately 3 times from baseline immediately after cardiac surgery, remained elevated on postoperative days 0, 1, and 2, and began to downtrend on postoperative day 3. Plasma renin activity was approximately 3 times higher at all measured time points in patients who developed vasoplegia versus those who did not. In patients undergoing cardiac surgery on cardiopulmonary bypass, plasma renin activity increased postoperatively and remained elevated through postoperative day 2. Additionally, patients with vasoplegic syndrome after cardiac surgery on cardiopulmonary bypass had more robust elevations in plasma renin activity than nonvasoplegic patients. These findings support the need for randomized controlled trials to determine if patients undergoing cardiac surgery with high plasma renin activity may benefit from targeted treatment with therapies such as synthetic angiotensin II.

Pseudohipoaldosteronism Type 1: a case report supported by a literature review

In the neonatal period, hydro electrolytic disorders with dehydration and metabolic acidosis can cause admission to an intensive care unit and become a diagnostic challenge. Among such disorders, hyponatremia and hyperkalemia become diagnostic challenges with hormonal involvement, including aldosterone. Pseudohypoaldosteronism (PHA) resulting from the lack of response to aldosterone in target cells can be classified into three types and its suspected diagnosis in cases of hyponatremia, hyperkalemia with an elevation of serum aldosterone, can be confirmed by exome sequencing with identification of a potentially pathogenic. This study was based on the case report of a newborn of consanguineous parents who, after birth, evolved in the first week of life with shock, hyponatremia, hyperkalemia, and metabolic acidosis. An initial investigation ruled out congenital adrenal hyperplasia. The presence of hyperaldosteronism with increased plasma renin activity, associated with hyperkalemia and hyponatremia difficult to control with electrolyte replacement, led to a molecular investigation that confirmed PHA type 1 by a mutation in the SCCN1A gene. In neonates with severe hyponatremia that is difficult to resolve with conventional treatment and elevation of serum aldosterone, this pathology must be remembered and investigated, avoiding high morbidity and mortality.

SGLT2 inhibitor and loop diuretic induce different vasopressin and fluid homeostatic responses in nondiabetic rats.

Loop diuretics are commonly used diuretics in the treatment of fluid retention but induce hypovolemia-related renal dysfunction. Na+-glucose cotransporter 2 (SGLT2) inhibitors induce osmotic diuresis, but body fluid volume is maintained by stimulating vasopressin-induced fluid intake and collecting duct water reabsorption as previously reported in diabetic rats. We aimed to test the hypothesis that unlike SGLT2 inhibitors, loop diuretics lack activation of similar fluid homeostatic mechanisms. Nondiabetic male Sprague-Dawley rats were treated daily by oral gavage with vehicle, the SGLT2 inhibitor ipragliflozin (5 mg/kg), or the loop diuretic furosemide (50 mg/kg) and monitored in metabolic cages for 2 or 7 days. Ipragliflozin and furosemide similarly increased urine volume on day 2. This was associated with increased serum Na+ concentration, urine vasopressin excretion, fluid intake, and solute-free water reabsorption in response to ipragliflozin but not to furosemide. Ipragliflozin maintained fluid balance (fluid intake - urine volume) on day 2 and total body water measured by bioimpedance spectroscopy and serum creatinine on day 7. In comparison, furosemide decreased fluid balance on day 2 and decreased total body water and increased serum creatinine on day 7. Furosemide, but not ipragliflozin, increased plasma renin activity, and systolic blood pressure was similar among the groups. In conclusion, the osmotic diuresis of the SGLT2 inhibitor increased serum Na+ concentration and the vasopressin-related stimulation of fluid intake and renal water retention maintained fluid balance, whereas the loop diuretic did not engage the compensatory vasopressin system. The data suggest differences in vasopressin and fluid homeostatic responses between SGLT2 inhibitors and loop diuretics.NEW & NOTEWORTHY In nondiabetic rats, the Na+-glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin increased vasopressin-related stimulation of fluid intake and free water reabsorption and maintained fluid balance and serum creatinine, whereas the loop diuretic furosemide reduced vasopressin and induced a negative fluid balance followed by a subsequent increase in serum creatinine. This study suggests that differences in vasopressin secretion in response to a SGLT2 inhibitor or loop diuretic may contribute to differences in body fluid status and subsequent renal function.

IMPROVEMENT OF LEFT VENTRICULAR SYSTOLIC DYSFUNCTION AFTER TREATMENT FOR PRIMARY ALDOSTERONISM CORRELATES WITH REVERSAL OF RENIN SUPPRESSION

Objective: Primary aldosteronism (PA) leads to hypertension, left ventricular hypertrophy and systolic dysfunction. While treatment can lead to regression of left ventricular mass, improvement of left ventricular function has not been demonstrated, using the conventional left ventricular ejection fraction for assessment. We used speckle-tracking echocardiography to assess if treatment of PA can improve left ventricular subclinical systolic dysfunction. Design and method: We prospectively recruited 57 patients with PA. All patients underwent 24–hours ambulatory blood pressure (BP) measurements and 2D echocardiography, including global longitudinal strain (GLS), at baseline and 12 months after surgical or medical therapy. Results: Forty–eight of 57 patients underwent adrenal vein sampling, and all procedures were successful. Twenty–five patients underwent unilateral adrenalectomy, and 32 patients were treated with medications. Patients treated with surgery had improved daytime systolic and diastolic BP, with reduced antihypertensive medications, while patients on medications had improved daytime systolic BP, with increased medications. While left ventricular ejection fraction did not change in either group post-treatment, GLS improved post–adrenalectomy by –2.3, 95%CI: –3.9 to –0.6, P = 0.0095, and post–medications by –1.3, 95%CI: –2.6 to 0.03, P = 0.089. On multivariate analysis, baseline GLS was associated with baseline diastolic BP (P = 0.019). Post–adrenalectomy, there were also improvements in left ventricular mass index by –10, 95% CI: –18.0 to –2.4, P = 0.012 left atrial volume index by –5.0, 95%CI: –9.1 to –2.2, P = 0.0016 and mitral E/e’ –1.9, 95%CI: –4.1 to –0.5, P = 0.0064, which were not significant in patients treated medically. Improvement in GLS was independently correlated with baseline GLS (P = 0.0001), and increase in plasma renin activity (P = 0.0068). Conclusions: Treatment of hyperaldosteronism can effectively reverse left ventricular systolic dysfunction, with greater benefit seen with surgery compared to medications. Greater improvement of systolic function is associated with increase in renin levels. This underlies the importance of adequate treatment to reverse the sodium overload state, that is the hallmark of PA.

Resemblance in Physiological Systems during Phylogeny and Ontogeny

Although it is not certain whether some characteristics of the mammalian fetus/embryo may repeat the adult stage of ancestral vertebrates, comparison of these two time‐dependent processes should provide new insight into the molecular and functional evolution and its significance. Here we discuss two important biological models: 1) Renin‐angiotensin system (RAS) and 2) Urine concentration mechanism.Renin is a hormone and substrate‐dependent enzyme secreted mostly by the juxtaglomerular (JG) cells of the afferent arteriole located at the vascular pole of the glomerulus. Renin acts on renin substrates and forms angiotensin (Ang) I which is subsequently converted to Ang II by Ang converting enzyme (ACE). Renin containing cells evolved early both in phylogeny and ontogeny, whereas, the macula densa (tubule component), and extracellular mesangium appeared at later stages.Renin containing cells are distributed more widely intrarenally and/or extrarenally in early stages during phylogeny and ontogeny. Granulated cells and renin expression become progressively restricted to JG areas with phylogenic and ontogenic advancement. Kidney renin activities tend to be higher in primitive fishes than in more advanced, while the relative level of extrarenal renin expression to that of the kidney is higher in embryos than in more mature chicken and mice. Extra renal renin is noted in primitive vertebrates. Also, in both the mammalian fetus and nonmammalian vertebrates, the vasopressor and vascular action of Ang II evolved early. A single application of ACE inhibitors decreases the basal level of blood pressure and increase plasma renin activity in conscious adult teleost fish. Ang II stimulates, whereas ACE inhibitors inhibit, arteriolar branching in zebrafish. Likewise, the RAS is important during early ontogeny of mammals in vascular growth and development.Distal tubules of freshwater trout show secondary active NaCl cotransport mechanism without accompaniment of water and act as the so‐called “diluting segment.” Teleost fish cannot concentrate urine because they lack structural and functional countercurrent mechanisms. Only birds and mammals can form urine clearly hyperosmotic to plasma and conserve body water. The structure and function of adult quail kidneys have similarities to those of developing rodents. Both have a loop of Henle, consisting of descending limb and thick ascending limb, but they lack the thin ascending limb. Countercurrent urine concentration of adult quail and developing rodents heavily depends on NaCl recycling without participation of urea transport. Moreover, in both adult quail and developing rodent kidneys, aquaporin 2 gene expression and protein are present in the apical membrane of the collecting tubules, but the water conservation effect of neurohypophysial hormones is smaller than that of adult rodent kidneys. Hence, comparing these two time‐dependent processes may provide new insights into the interpretation of existing findings and provide perspective for future investigations.

The role of Plasma Renin Activity in prenatally diagnosed non-obstructed hydronephrosis at risk for surgery-an observational study.

Patients with asymptomatic prenatally diagnosed hydronephrosis may progress to needing surgery; no biomarker supporting the identification of these cases is currently available. The aim of the study wasto assess the role of Plasma Renin Activity (PRA) as a discriminatory factor to identify patients with asymptomatic prenatally diagnosed hydronephrosis who require close monitoring and are at-risk for surgery. The study group consists of 30 children prenatally diagnosed with asymptomatic unilateral hydronephrosis, initially managed with medical follow-up. Pyeloplasty was indicated if patients became symptomatic or if there was a significant drop in split renal function (SRF) during follow-up. An association was sought between PRA and renal parameters in post-hoc analysis. During the mean follow-up of 55.5 ± 8.2months, 13/30 (43.3%) patients developed delayed drainage and 8/30 (26.6%) underwent pyeloplasty. Mean PRA was higher at presentation in the group which later presented with a drop in differential kidney function ≥ 10%, while it was within the normal range for age in the other patients. Before pyeloplasty, progression to delayed drainage coincided with a drop in SRFand a rise in PRA. While PRA levels normalized after pyeloplasty, SRF improved but did not reach initial values. A mean rise of 68.9% in PRA preceded current indications for surgery by 27.5 ± 9.5months. A progressive increase in PRA in children with asymptomatic prenatally diagnosed hydronephrosis reflects obstructive stress in the tubulo-interstitial compartment. This stress is relieved by pyeloplasty and is reflected by a drop in PRA after surgery. PRA can, thus, serve as the discriminatory factor to identify hydronephrosis patients 'at-risk' for surgery even before the current criteria for pyeloplasty are met.

Effect of the Renin-Angiotensin-Aldosterone System Reactivity on Endothelial Function and Modulative Role of Valsartan in Male Subjects with Essential Hypertension.

Background: The aim of the study was to evaluate the relationship between renin-angiotensin-aldosterone (RAA) system activity and reactivity, and the endothelial function profile in normotensive subjects (N), and in essential hypertensives (H), followed by analysis of the modulatory role of an angiotensin receptor blocker (ARB): valsartan, administered in the management of hypertension. Methods: A total of 101 male subjects were enrolled to the study: 31H and 70N. The nitric-oxide (NO) bioavailability (l-Arginine, asymmetric dimethylarginine (ADMA)), symmetric dimethylarginine (SDMA), endothelial vasodilative function (flow mediated dilation (FMD)), oxidative-stress markers (malonyldialdehyde (MDA), thiol index (GSH/GSSG), nitrotyrozine (N-Tyr)), and pro-inflammatory/angiogenic parameters (sICAM-1, sVCAM-1, PAI-1, sE-selectin, PAI-1, thromboxane -B2) were assessed at baseline, then after intravenous -l-arginine administration, which was repeated after the 4-day acetylsalicylic acid (ASA) administration (75 mg/24 h). In hypertensives, this whole protocol was repeated following 2 weeks of valsartan therapy. Results: No effect of valsartan and ASA on the flow-mediated vasodilation (FMD) and the NO bioavailability in hypertensives was observed. Administration of valsartan increased plasma renin activity (PRA), but without a decrease in the aldosterone levels. ASA treatment minimized the pre-existing differences between the groups, and increased the PRA in the N-subgroup with the highest ARR values. The blood concentrations of proinflammatory sICAM-1, sE-selectin, sVCAM-1, and PAI-1 were higher, whereas the anti-inflammatory 6-keto-PGF1 alpha level was lower in hypertensive subjects. The levels of angiogenic VEGF did not differ between groups. Conclusions: Our study does not confirm the modulative effect of valsartan on endothelial function. Normotensive men showed an increase in FMD after l-arginine administration, possibly indicating baseline impairment of the NO synthesis.

Psoriasis Relationship with Hypertension in Psoriasis Patients at RSI Jemursari Surabaya

Abstract. Background: Psoriasis is a chronic inflammatory disease of the skin that characterized by firmly bound erythema plaques covered in thick squama and caused by multiple abnormalities of genetic, biochemical, immunologic, vascular with further severed by various other factors such as psychology, drugs, smoking, and alcohol consumption. Several studies revealed that psoriasis can increase the risk of cardiovascular diseases such as hypertension, however, the underlying pathophysiological mechanism has not been confirmed yet. This mechanism is probably attributed to increased levels of angiotensin-converting enzyme produce angiotensin II that regulates vascular tonus, endothelin-1 (ET-1) has been considered an important role in that vasoconstrictor proteins are potent, and increased plasma renin activity has been reported in patients with psoriasis. Purpose: In order to figure out the relationship between psoriasis and hypertension in psoriasis patients at the Outpatient Unit -RSI Jemursari Surabaya. Methods: This study was observational analytics with cross sectional study design in 28 psoriasis patients at Outpatient Unit-RSI Jemursari Surabaya during 2017-2019, using total sampling technique. Secondary data from medical records was collected and further analyzed with spearman correlation tests. Result: The obtained significance value is 0.000 (p &lt; 0.05), which represent a significant relationship between hypertension and psoriasis. the correlation coefficient is 0.757, which indicates the strength of a strong relationship between two variables. Conclusion: There is a significant association between Psoriasis and Hypertension.

Effect of Mineralocorticoid Receptor Antagonism and ACE Inhibition on Angiotensin Profiles in Diabetic Kidney Disease: An Exploratory Study.

BackgroundRenin–angiotensin–aldosterone system (RAAS) blockade with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) is the cornerstone of antihypertensive treatment in patients with chronic kidney disease (CKD) and diabetes mellitus. Mineralocorticoid receptor antagonists (MRA) on top of conventional RAAS blockade confer cardio- and renoprotective effects. Yet, the detailed effects of this therapeutic approach on key RAAS effectors have not been elucidated to date.MethodsIn this exploratory placebo-controlled study, 15 patients with CKD stages 2–3 and albuminuria due to diabetic kidney disease (DKD) were randomized to receive the MRA eplerenone or placebo in addition to ACEi therapy. Employing mass-spectrometry, we quantified plasma angiotensin levels [Ang I, Ang II, Ang-(1–7), Ang-(1–5), Ang III, Ang IV], renin and aldosterone in patients before and after 8 weeks of MRA treatment.ResultsWhile blood pressure and kidney function were similar in the placebo and eplerenone treatment group during the study period, distinct differences in RAAS regulation occurred: eplerenone treatment resulted in an increase in plasma renin activity, Ang I and aldosterone concentrations, indicating global RAAS activation. In addition, eplerenone on top of ACEi profoundly upregulated the alternative RAAS effector Ang-(1–7).ConclusionsCombined eplerenone and ACEi therapy increases Ang-(1–7) levels in patients with CKD indicating a unique nephroprotective RAAS pattern with considerable therapeutic implications.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01118-7.

Descending thoracic aorta\u2013abdominal aortic bypass and bilateral renal arterial blood circulation reconstruction are effective in atypical coarctation of the aorta with heart failure: a case report

BackgroundThere are a lot of reports of the renal failure and heart failure due to coarctation of the aorta. However, there are no case reports in which revascularization dramatically improved left ventricular function in patients with progressive decline in left ventricular function. Herein, we present a rare case in which the left ventricular function was dramatically improved by surgical treatment for progressive left ventricular dysfunction due to atypical coarctation of the aorta.Case presentationA 58-year-old man underwent left axillary artery-bilateral femoral artery bypass at another hospital for atypical coarctation of the aorta due to Takayasu’s arteritis. Approximately 10 years later, he was re-hospitalized for heart failure, and the left ventricular ejection fraction gradually decreased to 28%. Computed tomography showed severe calcification and stenosis at the same site from the peripheral thoracic descending aorta to the lower abdominal aorta of the renal artery, and aortography showed delayed bilateral renal artery blood flow. An increase in plasma renin activity was also observed. Despite the administration of multiple antihypertensive drugs, blood pressure control was insufficient. We decided to perform surgical treatment to improve progressive cardiac dysfunction due to increased afterload and activated plasma renin activity. Descending thoracic aorta-abdominal aorta bypass and revascularization of the bilateral renal arteries via the great saphenous vein grafts were performed. Postoperative blood pressure control was improved, and the dose of antihypertensive drugs could be reduced. Plasma renin activity decreased, and transthoracic echocardiography 1.5 years later showed an improvement in contractility with a left ventricular ejection fraction of 58%.ConclusionIn atypical coarctation of the aorta in patients with decreased bilateral renal blood flow, heart failure due to renal hypertension, and progressive decrease in left ventricular contractility, descending thoracic aorta-abdominal aortic bypass and bilateral renal artery recirculation can be extremely effective.

LEVEL OF SODIUMURETIC PEPTIDE IN EARLY DIAGNOSIS OF CHRONIC HEART FAILURE IN PATIENTS WITH ARTERIAL HYPERTENSION

Chronic heart failure (CHF) is the most common and serious complication of cardiovascular disease. Arterial hypertension is the most common cause of CHF. The study of the problem of heart failure in the early stages of its development is of particular interest to clinicians. At the same time, the diagnosis of CHF in the early stages is important to prevent its further progression. To date, data have appeared on the possibility of early diagnosis of CHF of any etiology and predicting the occurrence of unfavorable outcomes of heart failure using brain natriuretic peptide - B - type Natriuretik Peptide (BNP) In recent years, as a marker of the early (preclinical) stage of CHF in patients with arterial hypertension group B natriuretic peptide (BNP) is used. Serum BNP is becoming the standard in the early diagnosis of CHF. The main stimulus for increased BNP secretion is left ventricular volume overload. Natriuretic peptides (NP) are physiological angiotensin II antagonists in relation to the stimulation of aldosterone secretion. An increase in plasma renin activity and aldosterone concentration causes left ventricular remodeling, accumulation of fibrous tissue, and ventricular overload. The main trigger for BNP is increased myocardial tension.

125 Increased plasma renin activity during wake in a repetitive sleep restriction protocol

Abstract Introduction Insufficient sleep is associated with an increased risk of hypertension. It is well established that long-term BP regulation is modulated by the renin-angiotensin-aldosterone system (RAAS) and chronic kidney disease is a strong independent risk factor for development of cardiovascular disease. This study investigated the biomarkers of RAAS and renal function during repetitive exposures to controlled, experimental sleep restriction (SR). We hypothesized an upregulation of RAAS and increased markers of impaired renal function. Methods Twenty-one healthy participants (11 women, average age 31±2 years) completed the 22-day in-hospital SR protocol: permitted 4h of sleep/night from 0300-0700 for 3 nights followed by a recovery sleep, repeated 4 times. Blood samples were collected and plasma renin activity (PRA) was assessed in the morning (7:05am) and in the evening before bedtime (22:45pm) at baseline, experimental days (3rd day of each of the 4 blocks), and recovery. Urinary albumin to creatinine ratio (ACR) was measured from 24-h urinary collection at baseline, first and fourth SR blocks. Estimated glomerulus filtration rate (eGFR) was calculated based on the serum cystatin C levels at baseline and last block of SR. Results Percent change of evening PRA significantly increased during 4 blocks of SR and recovery (SR effect p=0.039), but not morning PRA (SR effect p=0.34). Specifically, evening PRA increased up to 98.4% in the first (p&amp;lt;0.01), 61.3% in the second (p=0.04) SR blocks, and 57.5% (p=0.05) in recovery. Urinary ACR showed no significant changes during first or fourth SR blocks (SR effect p=0.28). In addition, eGFR did not change in the fourth SR block compared to BL (paired t-test, p=0.27). Conclusion We did not see increased markers of impaired renal function (ACR or eGFR). Rather, short-term repetitive exposures to SR significantly increased percent change of PRA measured before bedtime, and evening PRA did not return to BL level during recovery. Our results suggested that sleep deficiency may contribute to hypertension through upregulation of RAAS during wake time. Support (if any) SRSF (CDA to Huan Yang), NIH (R01HL106782 to Dr. Janet Mullington), Harvard Catalyst, Harvard Clinical and Translational Science Center (UL1TR001102).

The Effects of Short-Term Changes in Sodium Intake on Plasma Marinobufagenin Levels in Patients with Primary Salt-Sensitive and Salt-Insensitive Hypertension.

Increased marinobufagenin (MBG) synthesis has been suggested in response to high dietary salt intake. The aim of this study was to determine the effects of short-term changes in sodium intake on plasma MBG levels in patients with primary salt-sensitive and salt-insensitive hypertension. In total, 51 patients with primary hypertension were evaluated during acute sodium restriction and sodium loading. Plasma or serum concentrations of MBG, natriuretic pro-peptides, aldosterone, sodium, potassium, as well as hematocrit (Hct) value, plasma renin activity (PRA) and urinary sodium and potassium excretion were measured. Ambulatory blood pressure monitoring (ABPM) and echocardiography were performed at baseline. In salt-sensitive patients with primary hypertension plasma MBG correlated positively with diastolic blood pressure (ABPM) and serum NT-proANP concentration at baseline and with serum NT-proANP concentration after dietary sodium restriction. In this subgroup plasma MBG concentration decreased during sodium restriction, and a parallel increase of PRA was observed. Acute salt loading further decreased plasma MBG concentration in salt-sensitive subjects in contrast to salt insensitive patients. No correlation was found between plasma MBG concentration and left ventricular mass index. In conclusion, in salt-sensitive hypertensive patients plasma MBG concentration correlates with 24-h diastolic blood pressure and dietary sodium restriction reduces plasma MBG levels. Decreased MBG secretion in response to acute salt loading may play an important role in the pathogenesis of salt sensitivity.

A Low-Sodium Diet Boosts Ang (1-7) Production and NO-cGMP Bioavailability to Reduce Edema and Enhance Survival in Experimental Heart Failure.

Sodium restriction is often recommended in heart failure (HF) to block symptomatic edema, despite limited evidence for benefit. However, a low-sodium diet (LSD) activates the classical renin-angiotensin-aldosterone system (RAAS), which may adversely affect HF progression and mortality in patients with dilated cardiomyopathy (DCM). We performed a randomized, blinded pre-clinical trial to compare the effects of a normal (human-equivalent) sodium diet and a LSD on HF progression in a normotensive model of DCM in mice that has translational relevance to human HF. The LSD reduced HF progression by suppressing the development of pleural effusions (p < 0.01), blocking pathological increases in systemic extracellular water (p < 0.001) and prolonging median survival (15%, p < 0.01). The LSD activated the classical RAAS by increasing plasma renin activity, angiotensin II and aldosterone levels. However, the LSD also significantly up-elevated the counter-regulatory RAAS by boosting plasma angiotensin converting enzyme 2 (ACE2) and angiotensin (1–7) levels, promoting nitric oxide bioavailability and stimulating 3′-5′-cyclic guanosine monophosphate (cGMP) production. Plasma HF biomarkers associated with poor outcomes, such as B-type natriuretic peptide and neprilysin were decreased by a LSD. Cardiac systolic function, blood pressure and renal function were not affected. Although a LSD activates the classical RAAS system, we conclude that the LSD delayed HF progression and mortality in experimental DCM, in part through protective stimulation of the counter-regulatory RAAS to increase plasma ACE2 and angiotensin (1–7) levels, nitric oxide bioavailability and cGMP production.

Effect of diuretics on plasma renin activity in primary hypertension: A systematic review and meta-analysis.

Plasma renin activity (PRA) is regarded as a marker of sodium and fluid homeostasis in patients with primary hypertension. Whether effects of diuretics on PRA differ according to class of diuretic, whether diuretics lead to a sustained increase in PRA, and whether changes in PRA relate to those in blood pressure (BP) is unknown. We performed a systematic review and meta-analysis of trials investigating the antihypertensive effects of diuretic therapy in which PRA and/or other biomarkers of fluid homeostasis were measured before and after treatment. Three databases were searched: MEDLINE, EMBASE and The Cochrane Central Register of Controlled Trials. Titles were firstly screened by title and abstract for relevancy before full-text articles were assessed for eligibility according to a predefined inclusion/exclusion criteria. A total of 1684 articles were retrieved of which 61 met the prespecified inclusion/exclusion criteria. PRA was measured in 30/61 studies. Diuretics led to a sustained increase in PRA which was similar for different classes of diuretic (standardised mean difference [95% confidence interval] 0.481 [0.362, 0.601], 0.729 [0.181, 1.28], 0.541 [0.253, 0.830] and 0.548 [0.159, 0.937] for thiazide, loop, mineralocorticoid receptor antagonists/potassium-sparing and combination diuretics respectively, Q = 0.897, P = .826), and did not relate to the average decrease in blood pressure. In antihypertensive drug trials, diuretics lead to a sustained increase in average PRA, which is similar across different classes of diuretic and unrelated to the average reduction in blood pressure.

Low sodium intake increases plasma renin activity.

Reducing sodium intake to low levels (<2 g/day, 5 g/day of salt) is recommended in the entire adult population by the WHO [1], which will require substantial reductions in mean sodium intake globally (current mean: 3·9 g/day). The recommended low sodium intake target is based on short-term randomized clinical trials, reporting a reduction in blood pressure with reductions in sodium intake to low intake levels. It is assumed, but unproven, that sustained low sodium intake will translate into reductions in cardiovascular events, on the premise that reducing sodium intake will not have adverse effects.