Increased Renin Levels Research Articles

Excess renin is attributed to the combination of forward and backward failure in HFrEF.

Regulation of the renin-angiotensin system (RAS) in heart failure (HF) with reduced ejection fraction (HFrEF) still raises questions, as a large proportion of patients show normal renin levels despite manifest disease. Experimental venous congestion results in reduced renal perfusion pressure and stimulates renin secretion. We hypothesized that excess renin levels are mainly a result of right ventricular failure as a sequalae of left ventricular dysfunction. The study aimed to link right ventricular function (RVF) with renin levels and to investigate further contributors to excess RAS activation. Three hundred thirty-two chronic HFrEF patients undergoing routine ambulatory care were consecutively enrolled in a prospective, registry-based, observational study. Laboratory parameters, including cardiac-specific markers renin, aldosterone, and N-terminal pro-brain natriuretic peptide (NT-proBNP), echocardiographic examination (n=247), and right heart catheterization (n=85), were documented. The relationship between renin and its respective parameters was analysed. Renin concentration was not associated with the New York Heart Association class or NT-proBNP. Systolic blood pressure, systemic vascular resistance, serum sodium, aldosterone, and lactate dehydrogenase were associated with increased renin levels (P<0.035 for all). Renin levels similarly increased with worsening of RVF parameters such as fractional area change, tricuspid annular plane systolic excursion, tissue Doppler imaging, and inferior vena cava diameter (P<0.011 for all), but not with pulmonary pressure. Excess renin levels were observed when worsening RVF was combined with reduced renal perfusion {625μIU/mL [interquartile range (IQR): 182-1761] vs. 67μIU/mL [IQR: 16-231], P<0.001}, which was associated with worse survival. While unrelated to classical indices of HF severity, circulating renin levels increase with the worsening of RVF, especially in the combined presence of forward and backward failure. This might explain normal renin levels in HFrEF patients but also excess renin levels in poor haemodynamic conditions.

The role of renin-angiotensin system in sepsis-associated acute kidney injury: mechanisms and therapeutic implications.

This review aims to explore the relationship between the renin angiotensin system (RAS) and sepsis-associated acute kidney injury (SA-AKI), a common complication in critically ill patients associated with mortality, morbidity, and long-term cardiovascular complications. Additionally, this review aims to identify potential therapeutic approaches to intervene with the RAS and prevent the development of AKI. Recent studies have provided increasing evidence of RAS alteration during sepsis, with systemic and local RAS disturbance, which can contribute to SA-AKI. Angiotensin II was recently approved for catecholamine resistant vasodilatory shock and has been associated with improved outcomes in selected patients. SA-AKI is a common condition that can involve disturbances in the RAS, particularly the canonical angiotensin-converting enzyme (ACE) angiotensin-II (Ang II)/angiotensin II receptor 1 (AT-1R) axis. Increased renin levels, a key enzyme in the RAS, have been shown to be associated with AKI and may also guide vasopressor therapy in shock. In patients with high renin levels, angiotensin II administration may reduce renin concentration, improve intra-renal hemodynamics, and enhance signaling through the angiotensin II receptor 1. Further studies are needed to explore the role of the RAS in SA-AKI and the potential for targeted therapies.

Paeonol improves renal and vascular angiotensin II type 1 receptor function via inhibiting oxidative stress in spontaneously hypertensive rats

ABSTRACT Background Oxidative stress has been shown to play a critical role in the pathogenesis of hypertension. Paeonol, a major phenolic component extracted from Moutan Cortex, exerts a beneficial effect in preventing cardiovascular disease via reducing oxidative stress. The present study investigated the protective mechanism of paeonol against high blood pressure in spontaneous hypertension rats (SHRs). Methods Wistar-Kyoto (WKY) rats and SHRs received vehicle or peaonol in the drinking water for 5 weeks. Blood pressure was measured by tail-cuff plethysmography and oxidative stress in kidney and vascular tissue was examined by enzyme-linked immunosorbed assay. The functions of angiotensin II type 1 receptors (AT1R) in the kidney and mesenteric artery were measured by natriuresis and vasoconstrictor response, respectively. Results Compared with vehicle-treated WKY rats, vehicle-treated SHRs exhibited higher blood pressure, increased oxidative stress, accompanied by exaggerated diuretic and natriuretic responses to candesartan (AT1 receptor antagonist) and vasoconstrictor responses to angiotensin II (Ang II). Moreover, SHRs had higher ACE and AT1R in the kidney and mesenteric artery, and higher Ang II and lower renin levels. Interestingly, paeonol treatment reduced the candesartan-induced increase in diuresis and natriuresis and vasoconstrictor responses to Ang II, and lowered blood pressure in SHRs, accompanied by reducing AT1R protein expression in the kidney and mesenteric artery of SHR, and Ang II levels in plasma and increasing renin levels in renal cortex. In addition, these changes were associated with reducing oxidative stress. Conclusions The present study suggests that paeonol improves renal and vascular AT1R functions by inhibition of oxidative stress, thus lowering blood pressure in SHRs.

RAS-challenge as a first-look test for detection of primary aldosteronism in patients with treatment-resistant hypertension

Purpose Primary aldosteronism (PA), characterised by low-renin hypertension, confers a high cardiovascular risk and is the most common cause of secondary hypertension, with an increased prevalence in patients with treatment-resistant hypertension. However, it is estimated that only a small percentage of affected patients are identified in routine clinical practice. Inhibitors of the renin-angiotensin system cause an increase in renin levels in patients with intact aldosterone regulation, and inadequate low renin with concurrent RAS inhibition (RASi) may therefore indicate PA, which could serve as a first look screening test for selection for formal work-up. Methods We analysed patients between 2016–2018 with treatment-resistant hypertension who had inadequate low renin in the presence of RASi (i. e. at risk for PA) and who were offered systematic work-up with adrenal vein sampling (AVS). Results A total of 26 pts were included in the study (age 54.8 ± 11, male 65%). Mean office blood pressure (BP) was 154/95 mmHg on 4.5 antihypertensive drug classes. AVS had a high technical success rate (96%) and demonstrated unilateral disease in the majority of patients (57%), most of which (77%) were undetected by cross-sectional imaging. Conclusion In patients with resistant hypertension, low renin in the presence of RASi is a strong indicator for autonomous aldosterone secretion. It may serve as an on-medication screening test for PA to select for formal PA work up.

The levels of endothelin, renin, copeptin, testosterone, estradiol, osteocalcin and PIVKA-II in adolescents aged 17 years with newly diagnosed hypertension

Background. The purpose of the work is to study the blood content of biologically active substances — peptides and hormones that can affect blood pressure and the development of hypertension, depending on the gender and disease course in adolescents aged 17 years by comparing them with healthy individuals. Materials and methods. There were examined 87 adolescents (37 boys and 50 girls) who were divided into 4 main groups with stable and labile hypertension and 2 control groups with normotension. All patients underwent daily blood pressure monitoring and a comprehensive clinical examination, which ruled out symptomatic hypertension. The serum concentrations of biologically active substances were determined, namely endothelin, renin, copeptin, testosterone, estradiol, osteocalcin and protein induced by vitamin K absence (PIVKA-II), by enzyme immunoassay. Results. It was found that the most important feature that distinguishes hypertensive adolescents from normotensive peers was renin, which serum concentrations were almost 1.5 times higher in boys with labile hypertension and twofold — with stable hypertension. Girls with stable hypertension had the same patterns, with a twofold increase in renin level. Regardless of hypertension course, female adolescents had higher endothelin levels. In addition, girls with stable hypertension had high serum content of PIVKA-II. Conclusions. The elevated serum renin level in boys and girls at late stages of puberty as an indicator of renal dysfunction can be considered an essential cause of hypertension development. Determining the importance of renal dysfunction with increased levels of vasopressor hormones directs therapeutic efforts in the treatment of adolescents with hypertension precisely to the correction of this link in the pathogenesis of juvenile hypertension.

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.

The Association Between Angiotensin II and Renin Kinetics in Patients After Cardiac Surgery.

Hyperreninemia after cardiac surgery is associated with cardiovascular instability. Angiotensin II (AT-II) could potentially attenuate hyperreninemia while maintaining target blood pressure. This study assesses the association between AT-II usage and renin levels in cardiac surgery patients with postoperative hyperreninemia and vasoplegia. Between September 2020 and March 2021, we retrospectively identified 40 cardiac surgery patients with high Δ-renin levels (4 hours after cardiopulmonary bypass [CPB] minus preoperative levels) (defined as higher than 3.7 µU/mL) and vasopressor use who received a vasopressor therapy with either AT-II or continued norepinephrine alone. The primary outcome was the renin plasma level at 12 hours after surgery, adjusted by the renin plasma level at 4 hours after surgery. Overall, the median renin plasma concentration increased from a baseline with median of 44.3 µU/mL (Q1-Q3, 14.6-155.5) to 188.6 µU/mL (Q1-Q3, 29.8-379.0) 4 hours after CPB. High Δ-renin (difference between postoperation and preoperation) patients (higher than 3.7 µU/mL) were then treated with norepinephrine alone (median dose of 3.25 mg [Q1-Q3, 1.00-4.75]) or with additional AT-II (norepinephrine dose: 1.33 mg [Q1-Q3, 0.78-2.04]; AT-II dose: 0.34 mg [Q1-Q3, 0.29-0.78]). At 12 hours after surgery, AT-II patients had lower renin levels than standard of care patients (71.7 µU/mL [Q1-Q3, 21.9-211.4] vs 130.6 µU/mL [Q1-Q3, 62.9-317.0]; P = .034 adjusting for the renin plasma level at 4 hours after surgery). In cardiac surgery patients with hypotonia and postoperative high Δ-renin levels, AT-II was associated with reduced renin plasma levels for at 12 hours and significantly decreased norepinephrine use, while norepinephrine alone was associated with increased renin levels. Further studies of AT-II in cardiac surgery appear justified.

Estimation of Renin enzyme activity and some biochemical parameters among chronic renal failure patients in Tikrit city.

Chronic renal failure is a deficiency and failure in the excretory function of the kidneys, which causes a general imbalance in the body by retaining and accumulating nitrogenous waste and harmful substances as a result of metabolic reactions. Other functions of the kidneys, such as the regulation of fluids and electrolytes, may also be affected. This study's primary purpose is to estimate some parameters in the serum of chronic renal failure patients. Data and blood samples were obtained from 90 patients with chronic renal failure and 50 healthy volunteers for this cross-sectional study, conducted between 11 April and 26 July 2022. The results of this study show a considerable rise in the level of renin enzyme in patients (4.824±0.045) compared to the control (2.86±0.39), a high level of ALT in patients (19.56±8.13) compared to the control (11.24±0.98), high level of ALP in patients (95.34±67.71) compared to the control (38.81±5.14), high level of AST in patients (25.33±8.63) compared to the control (11.58±0.94), low level of albumin in patients with chronic renal failure (3.12±0.44) compared to the control (3.90±0.49), high level of globulin in patients with chronic renal failure (8.34±0.68) compared to the control (3.01±0.41), low level of calcium in patients with chronic renal failure (1.731±0.053) compared to the control (2.510±0.063), high level of potassium in the serum of patients with chronic renal failure (6.256±0.068) compared to the control (4.513±0.22), low level of sodium in patients with chronic renal failure (119.82±2.15) compared to the control group (143.76±2.11). According to this study, all physiological systems are significantly impacted by chronic renal failure. According to the results, chronic renal failure affects several electrolytes and liver function tests and causes a considerable increase in renin levels.

Malignant hypertension and hyperreninemia: primary or secondary hypertension? A case report

Malignant hypertension is a rare condition characterized by severe hypertension and multi-organ ischemic damage. Marked activation of the renin-angiotensin system is observed in many patients, but its persistence over time is not known. We report a case of a 42-year-old woman who presented with severe hypertension and multi-organ damage. Initial evaluation showed an elevated value of direct renin concentration with normal plasma aldosterone concentration and a nodular lesion in the left adrenal gland. The differential diagnosis between the primary and secondary form of hypertension had to be questioned. Consequently, the patient was followed up for 20 months. Repeated checks showed a significant increase in renin levels with a normal aldosterone concentration and regression of organ damage. After 20 months, renin values returned within normal range. Hyperreninemia persisting over a long period of time has not been fully explained. Long-term follow-up allowed us to attribute malignant hypertension to de novo essential hypertension.

Secondary hyperaldosteronism leading to resistant hypertension in a patient with adrenal Cushing’s syndrome

Background Cushing’s syndrome (CS) is a rare disorder caused by prolonged hypercortisolism leading to increased morbidity and mortality. Hypertension in Cushing’s syndrome could be caused by multiple mechanism including primary hyperaldosteronism from co-secretion of aldosterone from the adrenal tumour, and rarely due to secondary hyperaldosteronism. Case presentation A-36-year old female with poorly controlled hypertension, dyslipidaemia and diabetes mellitus presented with progressive truncal obesity with marked abdominal distension. She also had proximal muscle weakness and oligomenorrhea. On examination, specific clinical features suggestive of Cushing’s syndrome such as round face, facial plethora, truncal obesity with fat distribution in the face, neck, trunk, abdomen with sparing of the limbs, thin skin and proximal myopathy were present. Investigations confirmed the diagnosis of adrenocorticotrophic hormone independent adrenal Cushing’s syndrome due to a left adrenal adenoma with secondary hyperaldosteronism. Subsequently, she underwent laparoscopic left adrenalectomy as the definitive management which resulted in good clinical outcome. Conclusions Secondary hyperaldosteronism can be a rare association of Cushing’s syndrome and can contribute to resistant hypertension. Possible pathogenesis comprises of renin co-secretion, increased vascular responsiveness to vasopressor agents, increased renin levels leading to increased angiotensin 1 formation and possible interference of aldosterone action by steroids. Successful treatment of the primary pathology results in cure of the abnormality.

Mineralocorticoid Dysfunction during Critical Illness: A Review of the Evidence.

The recent demonstration of the significant reduction in mortality in patients with septic shock treated with adjunctive glucocorticoids combined with fludrocortisone and the effectiveness of angiotensin II in treating vasodilatory shock have renewed interest in the role of the mineralocorticoid axis in critical illness. Glucocorticoids have variable interactions at the mineralocorticoid receptor. Similarly, mineralocorticoid receptor-aldosterone interactions differ from mineralocorticoid receptor-glucocorticoid interactions and predicate receptor-ligand interactions that differ with respect to cellular effects. Hyperreninemic hypoaldosteronism or selective hypoaldosteronism, an impaired adrenal response to increasing renin levels, occurs in a subgroup of hemodynamically unstable critically ill patients. The suggestion is that there is a defect at the level of the adrenal zona glomerulosa associated with a high mortality rate that may represent an adaptive response aimed at increasing cortisol levels. Furthermore, cross-talk exists between angiotensin II and aldosterone, which needs to be considered when employing therapeutic strategies.

Clinical Characteristics of Aldosterone Producing Adenoma and Idiopathic Hyperaldosteronism with Obstructive Sleep Apnea Hypopnea Syndrome

To investigate the clinical characteristics of aldosterone producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) complicated with obstructive sleep apnea hypopnea syndrome (OSAHS) and the effect of OSAHS on renin-angiotensin-aldosterone system (RAAS) in APA and IHA patients. The clinical data of 127 patients with primary aldosteronism (PA) diagnosed from May 2010 to Aug. 2019 were retrospectively analyzed. There were 70 cases of APA, 53 cases of IHA. Another 4 cases were primary adrenal hyperplasia (PAH), so not included into further analysis. According to the results of polysomnography, the 123 patients of APA or IHA were divided into OSAHS group (96 cases) and non-OSAHS group (27 cases ). The patients with OSAHS were divided into mild, moderate and severe subgroups based on apnea hypopnea index (AHI).The clinical characteristics, biochemical parameters, plasma renin activity, aldosterone levels, and the ratio of aldosterone to renin activity (ARR) in the patients of APA and IHA complicated with OSAHS were compared with those of the patients without OSAHS. There were 49 OSAHS cases (49/70, 70.0%) in APA patients. and 47 OSAHS cases (47/53, 88.7%) in IHA patients. The age, male ratio, body mass index (BMI), waist circumference, triglyceride, blood uric acid, and blood creatinine in APA patients with OSAHS were higher than those in APA patients without OSAHS ( P<0.05), while high-density lipoprotein and estimated glomerular filtration rate (eGFR) were lower ( P<0.05). Compared to the patients without OSAHS, IHA-OSAHS patients had higher BMI and waist circumference ( P<0.05). Moderate/severe OSAHS-APA patients exhibited higher plasma renin activity levels and lower ARR values than the APA patients with no/mild OSAHS ( P<0.05). There were no significant differences in plasma renin activity, aldosterone levels, and ARR values between moderate/severe OSAHS-IHA group and no/mild OSAHS-IHA group. The prevalence of OSAHS is significantly higher in the patients with PA than normal population, and OSAHS may aggravate glycose, lipid and uric acid metabolism in PA patients. Moderate/severe OSAHS can increase renin levels and decrease ARR values in APA patients, but has no significant effect on RAAS in IHA patients.

Cardiac Inflammation after Ischemia-Reperfusion of the Kidney: Role of the Sympathetic Nervous System and the Renin-Angiotensin System.

To investigate the role of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in renal ischemia/reperfusion-induced (I/R) cardiac inflammatoryprofile. Left kidney ischemia was induced in male C57BL/6 mice for 60 min, followed by reperfusion for 12 days, and treatment with or without atenolol, losartan, or enalapril. The expression of vimentin in kidney and atrial natriuretic factor (ANF) in the heart has been investigated by RT-PCR. In cardiac tissue, levels of β1-adrenoreceptors, adenylyl cyclase, cyclic AMP-dependent protein kinase (PKA), noradrenaline, adrenaline (components of SNS), type 1 angiotensin II receptors (AT1R), angiotensinogen/Ang II and renin (components of RAS) have been measured by Western blotting and HPLC analysis. A panel of cytokines - tumour necrosis factor (TNF-α), interleukin IL-6, and interferon gamma (IFN-γ) - was selected as cardiac inflammatory markers. Renal vimentin mRNA levels increased by >10 times in I/R mice, indicative of kidney injury. ANF, a marker of cardiac lesion, increased after renal I/R, the values being restored to the level of Sham group after atenolol or enalapril treatment. The cardiac inflammatory profile was confirmed by the marked increase in the levels of mRNAs of TNF-α, IL-6, and IFN-γ. Atenolol and losartan reversed the upregulation of TNF-α expression, whereas enalapril restored IL-6 levels to Sham levels; both atenolol and enalapril normalized IFN-γ levels. I/R mice showed upregulation of β1-adrenoreceptors, adenylyl cyclase, PKA and noradrenaline. Renal I/R increased cardiac levels of AT1R, which decreased after losartan or enalapril treatment. Renin expression also increased, with the upregulation returning to Sham levels after treatment with SNS and RAS blockers. Angiotensinogen/Ang II levels in heart were unaffected by renal I/R, but they were significantly decreased after treatment with losartan and enalapril, whereas increase in renin levels decreased. Renal I/R-induced cardiac inflammatory events provoked by the simultaneous upregulation of SNS and RAS in the heart, possibly underpin the mechanism involved in the development of cardiorenal syndrome.

Treatment of Primary Aldosteronism with mTORC1 Inhibitors

CONTEXT Mammalian target of rapamycin complex 1 (mTORC1) activity is often increased in the adrenal cortex of patients with primary aldosteronism (PA), and mTORC1 inhibition decreases aldosterone production in adrenocortical cells, suggesting the mTORC1 pathway as a target for treatment of PA. OBJECTIVE To investigate the effect of mTORC1 inhibition on adrenal steroid hormones and hemodynamic parameters in mice and in patients with PA. DESIGN (i) Plasma aldosterone, corticosterone, and angiotensin II (Ang II) were measured in mice treated for 24 hours with vehicle or rapamycin. (ii) Plasma aldosterone levels after a saline infusion test, plasma renin, and 24-hour urine steroid hormone metabolome and hemodynamic parameters were measured during an open-label study in 12 patients with PA, before and after 2 weeks of treatment with everolimus and after a 2-week washout. MAIN OUTCOME MEASURES (i) Change in plasma aldosterone levels. (ii) Change in other steroid hormones, renin, Ang II, and hemodynamic parameters. RESULTS Treatment of mice with rapamycin significantly decreased plasma aldosterone levels (P = 0.007). Overall, treatment of PA patients with everolimus significantly decreased blood pressure (P < 0.05) and increased renin levels (P = 0.001) but did not decrease aldosterone levels significantly. However, prominent reduction of aldosterone levels upon everolimus treatment was observed in four patients. CONCLUSION In mice, mTORC1 inhibition was associated with reduced plasma aldosterone levels. In patients with PA, mTORC1 inhibition was associated with improved blood pressure and renin suppression. In addition, mTORC1 inhibition appeared to reduce plasma aldosterone in a subset of patients.

Treatment of Primary Aldosteronism with mTORC1 Inhibitors

Primary aldosteronism is the most frequent cause of endocrine hypertension. It is characterized by inappropriately high and relatively autonomous aldosterone production by the adrenal cortex Treatment of primary aldosteronism by unilateral adrenalectomy or mineralocorticoid receptor antagonists is not always well tolerated, and targeted pharmacological aldosterone-lowering therapies are still lacking. The adrenal cortex of patients with primary aldosteronism commonly shows increased mTORC1 activity, and mTORC1 inhibition decreases aldosterone production in adrenocortical cells. Here, we show that treatment of mice with rapamycin decreases plasma aldosterone levels, without affecting other steroid hormones. Furthermore, treatment of patients affected by primary aldosteronism with everolimus significantly decreased blood pressure and increased renin levels along with a reduction in aldosterone levels in a subset of patients. These findings suggest a role of mTORC1 in primary aldosteronism and that a subset of patients with this condition may benefit from drugs targeting the mTORC1 pathway. Clinical Trial Number: The trial was registered at Clinicaltrials.gov (NCT03174171) Funding Statement: M.N.H. and M.M.S. received funding from Novartis Foundation for Medical Biological Research, M.M.S. received funding from Novartis/University of Basel Excellence Scholarship for Life Sciences. A.O. received funding from the Swiss National Science Foundation (31003A179400). FB and MR have been supported by the Deutsche Forschungsgemeinschaft (DFG) within the CRC/Transregio 205/1 “The Adrenal: Central Relay in Health and Disease“ and by the Else Kroner-Fresenius Stiftung (2013_A182 and 2015_A171 to MR). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study was approved by the regional ethical committee (EKNZ 2015-400) and Swissmedic (2017DR2062), and was conducted in accordance with the guidelines for Good Clinical Practice and the Declaration of Helsinki. All animal experiments were approved by the Kantonales Veterinaramt of Kanton Basel-Stadt (Basel, Switzerland).

PP.28.29] THE ACUTE REDUCTION IN PLASMA POTASSIUM AND INCREASE IN RENIN LEVELS DURING AN ORAL GLUCOSE LOAD

PP.28.29] THE ACUTE REDUCTION IN PLASMA POTASSIUM AND INCREASE IN RENIN LEVELS DURING AN ORAL GLUCOSE LOAD

Impact of high-fat diet and hypoxia on the serum levels of main vasoconstrictors in male rabbits.

Introduction: During atherosclerosis process, vasoconstriction phenomenon occurs which in turn leads to tissue hypoxia. A few studies have been performed on the combination of atherosclerosis and hypoxia as stressors that may accelerate secretion of constrictors. The aim of present study was to evaluate the effects of atherosclerosis and hypoxia on serum levels of main vasoconstrictors (epinephrine, norepinephrine and renin). Methods: In this interventional study, 32 New Zealand white rabbits were randomly divided into four groups (n = 8): normal diet (control group), normal diet exposed to hypoxia (11%, 10 days), high-fat diet (cholesterol-2%, 8 weeks), and high-fat diet with hypoxia. Later, serum levels of renin, epinephrine and norepinephrine were measured on second, 56th and 66th days. Results: High-fat diet and hypoxia caused significant increase in epinephrine and norepinephrine concentrations on days 56 and 66 compared to the control group (P < 0.05). Also, renin showed significance increase in high-fat diet and high-fat diet+ hypoxia groups compared to the control group (P < 0.05). Conclusion: Both high-fat diet and hypoxia increase renin levels in male rabbits. Furthermore, the combination of high-fat diet and hypoxia immensely increases renin levels. Both hypoxia and combined of high-fat diet and hypoxia increase norepinephrine levels. However epinephrine is only increased in the combination of high-fat diet and hypoxia. So the presence of hypoxia in combination with high-fat diet, cause accelerated and aggravated atherosclerosis.

Hypertension Editors' Picks: Hypertension and Sleep.

Hypertension Editors' Picks: Hypertension and Sleep.

Low-Salt Diet and Circadian Dysfunction Synergize to Induce Angiotensin II-Dependent Hypertension in Mice.

Blood pressure exhibits a robust circadian rhythm in health. In hypertension, sleep apnea, and even shift work, this balanced rhythm is perturbed via elevations in night-time blood pressure, inflicting silent damage to the vasculature and body organs. Herein, we examined the influence of circadian dysfunction during experimental hypertension in mice. Using radiotelemetry to measure ambulatory blood pressure and activity, the effects of angiotensin II administration were studied in wild-type (WT) and period isoform knockout (KO) mice (Per2-KO, Per2, 3-KO, and Per1, 2, 3-KO/Per triple KO [TKO] mice). On a normal diet, administration of angiotensin II caused nondipping blood pressure and exacerbated vascular hypertrophy in the Period isoform KO mice relative to WT mice. To study the endogenous effects of angiotensin II stimulation, we then administered a low-salt diet to the mice, which does stimulate endogenous angiotensin II in addition to lowering blood pressure. A low-salt diet decreased blood pressure in wild-type mice. In contrast, Period isoform KO mice lost their circadian rhythm in blood pressure on a low-salt diet, because of an increase in resting blood pressure, which was restorable to rhythmicity by the angiotensin receptor blocker losartan. Chronic administration of low salt caused vascular hypertrophy in Period isoform KO mice, which also exhibited increased renin levels and altered angiotensin 1 receptor expression. These data suggest that circadian clock genes may act to inhibit or control renin/angiotensin signaling. Moreover, circadian disorders such as sleep apnea and shift work may alter the homeostatic responses to sodium restriction to potentially influence nocturnal hypertension.

Genetic Variants of C-5312T REN Increased Renin Levels and Diastolic Blood Pressure Response to Angiotensin Receptor Blockers.

Renin catalyzes the cleavage of angiotensinogen into angiotensin I. Genetic variant C-5312T of renin enhancer has been reported to increase in vitro renin gene transcription. However, no obvious in vivo study was performed to see the renin level in C-5312T when treated with angiotensin receptor blockers (ARB). Therefore, this study aimed to investigate the serum renin level and blood pressure response in ARB treated hypertensive patients. Single nucleotide polymorphism (SNP) of C-5312T was identified in 55 hypertensive patients by using multiplex PCR and renin serum level was assayed by ELISA. The data showed that the increase of serum renin levels after 5 months of ARB treatment was significantly higher in patients with CT/TT genotype (10 pg/mL) than those with CC genotype (4.08 pg/mL) (P = 0.025). Hypertensive patients with CT/TT genotypes also showed less diastolic pressure reduction than CC genotypes in hypertensive patients with valsartan treatment (P = 0.04) or telmisartan treatment (P = 0.03). Finally, these findings suggested that SNP of C-5312T REN enhancer might contribute to higher increased renin serum levels and less diastolic blood pressure response to ARB treatment.