Plasma renin activity and aldosterone concentration in children.

Using semi-micro methods, plasma renin activity (PRA) and plasma aldosterone concentration (PA) were measured concurrently in 79 healthy children aged 1 month to 15 years to establish a reference range. PRA and PA varied inversely with age. Eleven children with renal hypertension had higher PRA and PA than age-matched controls. In contrast, PRA was much greater in 38 saline-depleted children. PA was not uniformly increased in this group and was within the normal range in children with adrenal diseases compared with the high values seen in other salt-wasting states. The findings emphasise the need to relate data from patients to age-matched control values before attempting interpretation and suggest that sodium depletion is a more potent stimulator of renin-aldosterone release than renovascular disease or renal scarring in children. Plasma renin-aldosterone profiles were also valuable in discriminating between renal and adrenal causes of salt loss in childhood.     

肾血管性高血压和肾上腺腺瘤患者肾素-血管紧张素-醛固酮含量分析

目的 探讨肾素-血管紧张素-醛固酮系统、内皮素、一氧化氮在肾血管性高血压患者、肾上腺腺瘤患者中的作用和意义.方法 采用放射免疫分析的方法测量肾血管性高血压组(40例)、肾上腺腺瘤组(35例)和健康对照组(35例)血清肾素、血管紧张素Ⅱ、醛固酮、内皮素含量,用酶免疫法测定上述人群一氧化氮合酶(NOS)的含量来表示NO的量.结果 肾血管性高血压患者肾素、血管紧张素、醛固酮、内皮素含量高于健康对照组(P＜0.01),NOS含量低于健康对照组(P＜0.05);肾上腺腺瘤组醛固酮和内皮素含量高于健康对照组(P＜0.01),肾素、血管紧张素低于健康对照组(P＜0.05).结论 肾索、血管紧张素、醛固酮、内皮素和NO的检测可为临床早期诊断肾上腺腺瘤、肾血管性高血压提供依据.     

Aberrant Rac1–mineralocorticoid receptor pathways in salt‐sensitive hypertension

相似文献   

Pathogenesis of systemic (essential) hypertension in Zimbabwean hypertensive patients. I. Humoral factors.

Twenty-seven male and female black Zimbabweans hypertensive patients were matched by age and sex and compared to 27 normotensive subjects. All subjects were examined after dietary sodium depletion, followed by sodium loading. In addition to renin status and salt-sensitivity, urine aldosterone, renal prostaglandins, plasma atrial natriuretic peptide (ANP) and plasma endothelin were assessed. The following ethnic characteristics for Zimbabwean essential hypertensive patients were found: increased prevalence of salt-sensitive hypertension (66 pc); hyporesponsive renin-angiotensin system after contraction of circulating plasma volume; higher prevalence of low-renin hypertension (59 pc); suppressed renal prostaglandins, especially in low-renin hypertensives, suggesting suppression or deficit of renal kallikrein-kinin system; increased levels of ANP in low-renin hypertensive patients. Plasma endothelin was comparably increased in both normal- and low-renin hypertensive patients.     

Activity of the renin-angiotensin-aldosterone (RAA) and secretion of the atrial natriuretic peptide (ANP) in patients with chronic renal failure.

In 12 patients with chronic renal failure (CRF) treated with haemodialyses and in 21 healthy controls plasma renin activity (PRA) and the concentrations of aldosterone and atrial natriuretic peptide (ANP) were determined in serum before and after blockade of the angiotensin converting enzyme with captopril. The study was carried out under conditions of the so called bed rest test (BR) and water immersion test (WI). After captopril administration a significant rise of PRA was noted in both groups with a drop of aldosterone level which was significant only in the control group. Captopril administration had no effect on serum ANP level. The results of the study are not suggesting the presence of a close relationship between ANP secretion and the activity of the RAA system in healthy controls and in CRF patients.     

Cardiovascular and renal pathologic implications of prorenin, renin, and the (pro)renin receptor: promising young players from the old renin-angiotensin-aldosterone system

The overactivation of the renin–angiotensin–aldosterone system accounts for many cardiovascular and renal abnormalities. At several levels of its cascade, the renin–angiotensin–aldosterone system can be efficiently inhibited, of which interruption of the generation of angiotensin I by renin inhibition is considered most efficacious. All of these interruptions (renin inhibition, angiotensin-converting enzyme inhibition, and AT1 receptor blockade) increase plasma renin levels by inhibiting the negative feedback loop exerted by angiotensin II on renin production. Recent studies show that both prorenin and renin activate angiotensin II-independent signaling cascade through (pro)renin receptor, a new-fangled player of the old renin-angiotensin-aldosterone system. The probable mechanisms by which prorenin, renin, and (pro)renin receptors are functionally interrelated in pathophysiological conditions have been debated over the past decade without satisfactory conclusion. We revisited these areas and critically examined the relationship between elevated levels of circulating prorenin and renin-induced activation of the (pro)renin receptor and incidences of hypertension and end-organ damage. The complexity of the (pro)renin receptor has grown up with recent reports that this multifunctional receptor is a component of the Wnt receptor complex. This complexity and the receptor's function as an adaptor between the Wnt receptor and the vacuolar H+-ATPase complex has also been addressed in this review.     

Clinical effects of intravenous nifedipine on renal function

Nifedipine, a calcium antagonist, was administered intravenously (13.3 micrograms/min) for 45 min, and the changes in blood pressure, glomerular filtration rate (GFR), renal blood flow (RBF), total renal resistance, urinary volume, urinary sodium and potassium excretion, plasma renin activity, and plasma aldosterone concentration were studied. GFR and RBF were measured by intravenous infusion of sodium thiosulfate and sodium para-aminohippurate, respectively. The subjects included 12 cases of essential hypertension, nine of chronic glomerular nephritis with hypertension, 14 of chronic glomerular nephritis without hypertension, and 12 normotensive controls. In patients with essential hypertension, GFR and RBF increased markedly (by 45.6% and 44.8%, respectively), but in normotensive and hypertensive patients with chronic glomerular nephritis, these indices did not change significantly. The urinary volume and urinary sodium excretion increased in all groups. The natriuresis induced by nifedipine is probably due to the increase of GFR and RBF. The results of this study suggest a difference in renal vascular pathophysiology between essential hypertension and chronic glomerular nephritis. The results also suggest a functional change of the renal vascular system in essential hypertension, i.e., the increased vascular tone and the particular sensitivity of renal arterioles to nifedipine.     

肾性高血压大鼠胰岛素抵抗与肾间质纤维化相关研究

目的 从肾素.血管紧张素系统(RAS)角度初步探讨胰岛素抵抗(IR)对肾性高血压大鼠肾间质纤维化的影响.方法 SD大鼠行"两肾一夹"手术后随机分为蔗糖喂养组和对照组,蔗糖喂养组蔗糖喂养,对照组正常饲养,18周后处理.于处理前1日测定24 h尿蛋白定量;处理日测定2组血浆空腹血糖、胰岛素、胰岛素敏感指数、肾素、血管紧张素Ⅱ、醛固酮、尿素氮和肌酐水平.结果 与时照组相比,蔗糖喂养组空腹胰岛素水平明显增高(P<0.01),胰岛素敏感指数水平明显降低(P<0.01),血浆肾素、血管紧张素Ⅱ、醛固酮、尿素氮和肌酐水平及24 h尿蛋白定量均明显高于对照组(P<0.01).相关分析显示,24 h尿蛋白定量与血浆空腹胰岛素、胰岛素敏感指数、醛固酮及尿素氮水平呈明显相关.结论 IR状态能够加速肾性高血压大鼠肾间质纤维化的损害,除与血压升高、胰岛素的直接促增殖作用有关外,还可能与HIS引起的肾组织局部RAS的激活有关.     

Effect of benazepril monotherapy in subjects with hypertension associated with renal dysfunction

Nine hypertensive patients with mild to moderate renal dysfunction were entered into a protocol to assess the blood pressure, humoral and renal effects of the angiotensin converting enzyme inhibitor, Benazepril (CGS14824A, 2 to 20 mg twice daily) in patients with hypertension and moderate renal insufficiency (mean creatinine clearance 56 ml/min/1.73 m2). Specifically monitored, prior to and following 12 weeks of Benazepril monotherapy, were plasma renin activity and plasma aldosterone, the clearances of creatinine, Tc99m-diethylenetriaminepentaacetic acid (TC99m-DTPA) and para-amino-hippurate, and the 24-hour urinary excretion of protein. Blood pressure was well controlled. Plasma renin activity was stimulated, and plasma aldosterone was suppressed. Mean serum potassium increased from 3.9 to 4.2 mEq/L. Benazepril monotherapy had no adverse renal hemodynamic effect. Benazepril appears to be an effective antihypertensive agent in hypertensive patients with moderately impaired renal function.     

Acute changes in the renin-angiotensin-aldosterone system, catecholamines and prostaglandins during captopril in man

The acute hypotensive effect of 25 mg captopril was investigated in 26 hypertensive patients (11 essential and 15 with renal arterial disease). Intra-arterial blood pressure was recorded continuously and arterial blood was sampled for renin, angiotensin I and II, aldosterone, kininase II, catecholamines and prostaglandins. Captopril provoked increases in plasma renin activity, active and total plasma renin concentration and angiotensin I; decreases in plasma kininase II activity, angiotensin II, aldosterone, prostaglandins E2 and F2 alpha and no changes in plasma (nor)adrenaline, dopamine and inactive renin concentration.     

Renal vein renin measurements in children with hypertension.

Renal venous renin activity was measured in 50 children with hypertension. Main renal vein and segmental renal vein sampling was feasible in children as young as 15 months. In all cases in which there was a clear difference in renin secretion between the kidneys--that is, a main vein renin ratio above 1.5--surgery, when undertaken, successfully restored normal blood pressure. Most of the children with main renal vein renin ratios below 1.5 had bilateral disease or apparently normal kidneys. Segmental renal vein sampling contributed useful information additional to that provided by main renal vein measurements and permitted identification of local sources of renin production. In children with renal transplants who developed hypertension renal vein renin measurements helped in determining the cause and facilitating the management of the raised blood pressure.     

Studies with fenoldopam, a dopamine receptor DA1 agonist, in essential hypertension.

A series of studies were undertaken to assess the effect of oral fenoldopam, a specific DA1 dopamine receptor agonist on blood pressure and renal function in patients with mild essential hypertension. Six patients with essential hypertension were entered into a dose-ranging study and received either placebo, 25, 50 or 100 mg fenoldopam. A significant, dose-related reduction in diastolic blood pressure, and increase in heart rate was demonstrated (both P less than 0.05), maximal at 45 min to 1 h. Fenoldopam increased plasma renin activity. In a double-blind study, seven patients received a single dose of fenoldopam 100 mg or placebo. Fenoldopam produced a significant fall in systolic (P less than 0.05) and diastolic (P less than 0.01) blood pressure and renal vascular resistance (P less than 0.01). Urine flow rate (P less than 0.05), sodium excretion (P less than 0.01), plasma renin activity (P less than 0.05) and plasma aldosterone (P less than 0.05) increased. Five patients underwent measurement of the above parameters following a single dose of fenoldopam 100 mg with a repeat of these measurements after they had taken fenoldopam 100 mg four times daily for 1 month. The acute response of blood pressure to the single dose appeared unchanged but tachyphylaxis was evident in the responses of heart rate, plasma renin activity and plasma aldosterone.     

Is Primary Aldosteronism Underdiagnosed In Clinical Practice?

1. Primary aldosteronism is a syndrome consisting of hypertension, suppressed renin activity or concentration and high aldosterone levels in plasma or urine. The main steps in diagnosis are the determination of renin and aldosterone levels, the demonstration of renin-aldosterone dissociation and discrimination between idiopathic hyperplasia and Conn's adenoma, with only Conn's adenoma amenable to surgery. 2. Patients with resistant hypertension and/or hypokalaemia should be screened for primary aldosteronism with simple, redundant hormonal tests. The aldosterone to renin ratio is a logical initial screening test, a high ratio demonstrating renin-aldosterone dissociation. Criteria for a high ratio should be determined in each laboratory. 3. In patients with documented primary aldosteronism, computed tomography scan and adrenal vein sampling help to distinguish between idiopathic hyperplasia and Conn's adenoma. 4. Patients with low renin hypertension, idiopathic hyperplasia and Conn's adenoma have overlapping values for plasma concentrations of potassium, renin and aldosterone and the aldosterone to renin ratio. Because primary aldosteronism subtypes are quantitative diseases, the true prevalence of primary aldosteronism cannot be defined. 5. The use of sensitive screening tests (e.g. aldosterone to renin ratio) gives a higher prevalence of diagnosed cases of primary aldosteronism, but not of surgically correctable forms. Therefore, there is no clinical evidence that primary aldosteronism is underdiagnosed. 6. There is a need for tests to predict the postoperative blood pressure outcome of surgery in subjects with Conn's adenoma.     

BIOCHEMICAL CORRECTION IN THE SYNDROME OF HYPERTENSION AND HYPERKALAEMIA BY SEVERE DIETARY SALT RESTRICTION SUGGESTS RENIN-ALDOSTERONE SUPPRESSION CRITICAL IN PATHOPHYSIOLOGY

1. Plasma potassium and chloride concentrations were raised and plasma renin activity, aldosterone, bicarbonate and arterial pH were reduced in two brothers with the syndrome of hypertension and hyperkalaemia with normal glomerular filtration rate (Gordon's syndrome), on unrestricted or moderately restricted sodium diets. 2. These abnormalities were corrected in both patients within 10 days of severe sodium restriction. 3. Pressor sensitivity to cold and angiotensin II decreased on low sodium diet, associated with a fall in blood pressure. 4. Increasing distal tubular sodium delivery by infusion of normal saline increased fractional excretion of potassium when aldosterone had been stimulated by severely restricted sodium diet, but not when aldosterone levels were low on unrestricted sodium diet. 5. These findings are consistent with excessive sodium reabsorption as the primary renal lesion in Gordon's syndrome, leading to volume expansion and suppression of renin and aldosterone. Severe dietary sodium restriction leading to volume contraction, by stimulating renin and aldosterone and promoting kaliuresis, corrects the abnormalities.     

The development of the direct renin inhibitor aliskiren: treating hypertension and beyond

Background: Direct renin inhibitors such as aliskiren offer a novel way of treating hypertension and its co-morbidities, conditions with a considerable prevalence, morbidity, and mortality worldwide. Objective: The burden of hypertension worldwide and the role of the renin-angiotensin-aldosterone system in this disease will be reviewed. Current treatments for hypertension and its co-morbidities that work by manipulating this system will be discussed. The development of, and clinical trials involving, direct renin inhibitors will be reviewed, with a focus on aliskiren. Methods: PubMed was utilized to search the most recent literature on the topics of the renin-angiotensin-aldosterone system, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone and aliskiren. Results/conclusions: The direct renin inhibitors, including aliskiren, are new agents with great promise for the treatment of hypertension and its co-morbid conditions, including renal and cardiovascular disease.     

Renal and adrenal function following acute administration of urapidil in hypertensive patients with normal and impaired renal function

The effects of i.v. injection of urapidil (Ebrantil) (25 mg) on arterial blood pressure, renal function and renin-aldosterone system were studied in a group of patients with hypertension and normal renal function, in patients with hypertension and chronic renal failure and in normotensive controls. The pharmacokinetics of urapidil were evaluated simultaneously by measuring blood levels of the compound and its main metabolite. In the controls and in patients with hypertension, systolic and diastolic blood pressure were lowered few minutes after injection. Minimal blood pressure values were reached after 15-20 min. Hypotensive action was more pronounced in hypertensive patients as compared to controls. In contrast, increment in heart rate was greater in the controls. Despite the fall in blood pressure, renal plasma flow and glomerular filtration rate remained unchanged. Following the injection of urapidil, plasma renin activity increased with no change in plasma aldosterone levels. Plasma half-life of urapidil averaged 1.96 +/- 0.17 h in controls, 3.31 +/- 0.75 h in patients with hypertension and normal renal function and 2.52 +/- 0.46 h in patients with hypertension and chronic renal failure. Urapidil effectively lowers arterial blood pressure in patients with normal and impaired renal function with no deterioration in renal function.     

Which antihypertensive drugs are the most nephroprotective and why?

Importance of the field: Hypertension is a major independent risk factor for kidney disease and for faster renal function loss. Choice of antihypertensive strategies with highest nephroprotective effect is crucial to prevent or reverse progression to end stage renal disease (ESRD).

Areas covered in this review: The present review focuses on the role of hypertension in the progression of chronic kidney disease (CKD), the renoprotective effects of different antihypertensive therapies, and the blood pressure levels that should be targeted in different patient populations. To this end, the PubMed (1975 – 2010) database was searched for English-language articles, using the following keywords: hypertension, kidney disease, ACE-inhibitor, angiotensin receptor blocker, aldosterone antagonist, renin inhibitor, proteinuria.

What the reader will gain: A comprehensive review of data on the association between hypertension and progression of chronic nephropathies and on the antihypertensive treatments with highest nephroprotective effects.

Take home message: Blood pressure should be targeted to 140/90 mmHg or less in patients with hypertension but no renal injury and 130/80 mmHg or less in those with CKD. Amongst different antihypertensive drugs, renin angiotensin aldosterone system (RAAS) inhibitors have an incremental nephroprotective effect in proteinuric patients. Maximal RAAS inhibition should be aimed to optimize renoprotection in hypertensive patients with CKD and proteinuria.     

Stimulation of aldosterone secretion by metoclopramide is not affected by chronic converting enzyme inhibition

Summary To assess if dopaminergic control of aldosterone secretion is mediated by the renin-angiotensin system, the effect of chronic angiotensin converting enzyme inhibition by enalapril on the aldosterone response to metoclopramide has been studied in 10 patients with mild to moderate essential hypertension. Enalapril reduced supine blood pressure and increased the heart rate significantly. Plasma renin activity and urinary sodium excretion rose significantly. PRA was not changed by metoclopramide, neither during placebo nor during enalapril treatment. Metoclopramide induced a two-fold increase in plasma aldosterone, the peak response being reached within 15 min. Enalapril treatment did not alter the aldosterone response to metoclopramide. Dopaminergic control of aldosterone secretion appears to be independent of the renin-angiotensin system.     

Effect of metoprolol on 24-hour urinary excretion of adrenal steroids and kallikrein in patients with essential hypertension.

Treatment of fifteen patients with essential hypertension over four weeks using the beta 1-adrenoceptor blocking agent, metoprolol, resulted in a decrease in 24 h urinary excretion of kallikrein and aldosterone along with a decrease in plasma renin activity. There was no significant change in 24 h excretion rates of the free adrenal steroids deoxycorticosterone, 18-OH-deoxycorticosterone, corticosterone, cortisol or 18-OH-corticosterone during treatment, which were not significantly different from excretion rates of normal males, thus excluding inhibitory effects of adrenal steroids on urinary kallikrein activity. A positive correlation was found between plasma renin activity and urinary excretion of kallikrein during the control period and after 2 weeks on metoprolol, supporting the assumption of a preserved link between the renin-angiotensin-aldosterone system and the renal excretion of kallikrein in these patients. The decrease in kallikrein excretion during beta 1-adrenoceptor blockade in patients with essential hypertension may be explained by a reduction in sympathetic tone and by reduced activity of the renin-aldosterone system.     

The effects of lead on the renin-angiotensin system

Acute lead treatment of rabbits resulted in significant increases in both plasma renin activity and aldosterone concentration. No significant changes were observed in blood pressure, heart rate and plasma angiotensin-converting enzyme activity. The calcium channel-blocking drug verapamil attenuated the renin and aldosterone response in vivo. Lead increased renin release in a dose-dependent manner in a renal cortex slice preparation. Both verapamil and diltiazem attenuated the lead-induced renin release in vitro, but only with diltiazem did this attain statistical significance.