Higher Plasma Renin Activity Levels Research Articles

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.

Clinical characteristics of snoring patients with primary aldosteronism and obstructive sleep apnea\u2013hypopnea syndrome

The 2016 guideline on the work-up of primary aldosteronism recommended that patients with obstructive sleep apnea–hypopnea syndrome (OSAS) be screened. This study aimed to identify the clinical characteristics of snoring patients with primary aldosteronism (PA) complicated by OSAS. Sixty-eight self-reported or witnessed snoring patients and 609 non-snoring patients diagnosed with PA between 2010 and 2015 were recruited in this retrospective study. Compared to non-snoring patients, snoring patients had significantly (P < 0.05) higher body mass index (BMI), diastolic blood pressure (DBP), and serum and urinary sodium, as well as lower estimated glomerular filtration rate (eGFR). Moreover, snoring patients exhibited significantly (P < 0.01) higher plasma renin activity levels and lower plasma aldosterone levels and aldosterone-to-renin activity ratios (ARRs) than patients with PA alone. When age, sex, duration of hypertension, and BMI were matched between groups, snoring patients still showed significantly (P < 0.05) higher plasma renin activity, serum and urinary sodium, and lower ARR and eGFR than those in the PA-only group. All 68 snoring patients underwent polysomnography, with 7 having mild (apnea–hypopnea index (AHI) ≥ 5 and <15), 21 moderate (AHI ≥ 15 and <30), and 40 severe (AHI ≥ 30) OSAS. The BMI of patients with OSAS was negatively correlated with the lowest SaO2 (r = −0.318, P = 0.018) but not with the AHI. In conclusion, snoring patients with PA tend to have increased BMI and DBP, as well as decreased eGFR and ARR. Snoring patients with PA had higher prevalence of moderate-to-severe OSAS.

082 - Plasma Renin Activity in Distinct Patient Populations with Heart Failure and Reduced Ejection Fraction

Background: Renin-angiotensin-aldosterone system (RAAS) activation in heart failure with reduced ejection fraction (HFREF) is detrimental through cardiac remodeling and water/salt retention. Aims: This study aims to describe RAAS activity in distinct HFREF populations—acute decompensation, chronic HFREF and HFREF with normalized ejection fraction after cardiac resynchronization therapy (CRT)—and to assess its prognostic impact. Methods and Results: In 72 acute decompensated HFREF patients (ADHF), 78 chronic HFREF patients without clinical signs of congestion and 53 patients with HF with normalized ejection fraction (HFNEF), venous blood samples and hemodynamic parameters were obtained. Subjects were prospectively followed up to 30 months. Plasma renin activity (PRA) is significantly lower in ADHF (1.5 ng/ml/h [0.8;5.7]) compared to stable HFREF (7.6 ng/ml/h [2.2;18.1] and HFNEF patients (3.9 ng/ml/h [1.0;13.0]) (all P < .05) (Fig. 1). PRA was significantly associated with arterial blood pressure, renin-angiotensin system blocker dose, beta-blocker dose, and mineralocorticoid receptor antagonist use (all P < .05) but not with age, left ventricular ejection fraction, heart rate, loop diuretic dose, creatinine or NT-pro BNP (all P > .05). High PRA levels are associated with increased cardiovascular mortality or HF admission in acute ADHF, but not in stable HFREF or HFNEF (Fig. 2). Conclusion: PRA is significantly elevated in ambulatory chronic HFREF patients, even when ejection fraction has normalized after CRT which is associated with blood pressure and medication use. Yet, in contrast to ADHF where PRA levels predict cardiovascular mortality and rehospitalizations, PRA levels are not associated with outcome in chronic HFREF and HFNEF.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Pharmacogenetics of Antihypertensive Therapies: Can this be Applied in the Clinic?

Blood pressure responses to antihypertensive drugs vary widely between individuals. Certain phenotypic factors may predict some drug responses such as plasma renin activity (PRA) as an indicator of activation of the reninangiotensin- aldosterone system. Higher PRA levels may predict better average responses to angiotensin converting enzyme inhibitors, angiotensin receptor blockers or β-blockers. Conversely, high salt intake or salt sensitivity may predict a better response to diuretics and calcium channel blockers. Genetic factors influencing the pharmacokinetics of specific drugs through enzymes or transporters or the pharmacodynamics of drug classes through receptors or pathways involved in the mechanism of drug action can also affect blood pressure responses, but the effects of most candidate genes are limited. Furthermore, the need to choose the most effective first-line antihypertensive agent becomes less critical with the awareness that most hypertensive patients will require a combination of drugs and drug combinations with complementary modes of action should help to overcome the major mechanisms driving hypertension. However, there may be situations where genotypes in pathways that may not be directly related to the blood pressure lowering effect may predict cardiovascular benefits with certain drugs. Currently, there are probably no genetic factors which dictate the use of a particular antihypertensive drug, except in some of the rare monogenic causes of hypertension. With the rapid expansion of pharmacogenetic knowledge, this situation is likely to change and specific targeted treatments may be selected based on combined genetic and phenotypic factors for individualizing long-term therapy for hypertension. Keywords: Angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, diuretics, pharmacogenetics, phenotype, plasma renin activity.

Short-term vitamin D3 supplementation lowers plasma renin activity in patients with stable chronic heart failure: An open-label, blinded end point, randomized prospective trial (VitD-CHF trial)

Many chronic heart failure (CHF) patients have low vitamin D (VitD) and high plasma renin activity (PRA), which are both associated with poor prognosis. Vitamin D may inhibit renin transcription and lower PRA. We investigated whether vitamin D3 (VitD3) supplementation lowers PRA in CHF patients. We conducted a single-center, open-label, blinded end point trial in 101 stable CHF patients with reduced left ventricular ejection fraction. Patients were randomized to 6 weeks of 2,000 IU oral VitD3 daily or control. At baseline, mean age was 64 ± 10 years, 93% male, left ventricular ejection fraction 35% ± 8%, and 56% had VitD deficiency. The geometric mean (95% CI) of 25-hydroxyvitamin D3 increased from 48 nmol/L (43-54) at baseline to 80 nmol/L (75-87) after 6 weeks in the VitD3 treatment group and decreased from 47 nmol/L (42-53) to 44 nmol/L (39-49) in the control group (P < .001). The primary outcome PRA decreased from 6.5 ng/mL per hour (3.8-11.2) to 5.2 ng/mL per hour (2.9-9.5) in the VitD3 treatment group and increased from 4.9 ng/mL per hour (2.9-8.5) to 7.3 ng/mL per hour (4.5-11.8) in the control group (P = .002). This was paralleled by a larger decrease in plasma renin concentration in the VitD3 treatment group compared to control (P = .020). No significant changes were observed in secondary outcome parameters, including N-terminal pro-B-type natriuretic peptide natriuretic peptide and fibrosis markers. Most CHF patients had VitD deficiency and high PRA levels. Six weeks of supplementation with 2,000 IU VitD3 increased 25-hydroxyvitamin D3 levels and decreased PRA and plasma renin concentration.

Renin-Angiotensin System Blockers May Create More Risk Than Reward for Sodium-Depleted Cardiovascular Patients With High Plasma Renin Levels

Four recent reports revealed differences in survival rates among treated cardiovascular patients taking renin-angiotensin system-blocking drugs. Patients with higher on-treatment plasma renin activity (PRA) levels died sooner of cardiovascular mortality than those with lower levels. We investigated whether excessive sodium depletion might have induced the higher PRA levels and contributed to the greater morbidity and mortality. Using published data, ranges of PRA, blood pressures, drug usage, and biochemical parameters were compared among various groups of cardiovascular patients. We showed (i) that PRA levels are usually medium to low in treated cardiovascular patients, but are sometimes abnormally high, (ii) that excessive sodium depletion can induce such high PRA levels, (iii) that the higher PRA patients exhibited evidence of sodium depletion: lower blood pressures, more frequent natriuretic drug usage, lower N-terminal pro b-type natriuretic peptide (NT-proBNP), and higher blood urea nitrogen and uric acid levels, with similar usage of renin-angiotensin blocking drugs. We hypothesize that patients with high on-treatment PRA levels die sooner of cardiovascular events because they are excessively sodium-volume depleted. Moreover, renin-angiotensin system-blocking drugs may be harmful in such patients because they can functionally interfere with the effects of reactive rises in PRA that are triggered to prevent potentially dangerous falls in blood pressure, increases in plasma potassium, and falls in glomerular filtration rate. Careful liberalization of salt intake and subtraction of natriuretic drugs, sufficient to reduce reactive hyperreninemia without inducing unacceptable increases in blood pressure, might benefit such patients and decrease risk of adverse effects from drugs that block the renin-angiotensin system.

EFFECT OF NEDD4L GENE FIVE COMMON POLYMORPHISMS ON HYPERTENSION-RELATED PHENOTYPES IN HAN CHINESE HYPERTENSION PATIENTS

ObjectivesHypertension is a complex disorder; part is due to genetic determinants. Mounting evidence has suggested that NEDD4L plays a pivotal role in maintaining Na+ balance, extracellular fluid volume and long...

Influence of Salt Intake on Target Organ Damages in Treated Hypertensive Patients

This study investigates the influence of salt intake on renin–angiotensin–aldosterone system and clarifies their role to the target organ damage in the treated hypertensive patients. Subjects were 188 treated hypertensive outpatients (96 females and 92 males, mean age 67 ± 11 y). Patients underwent 24-hour home urine collection to measure urinary salt excretion and proteinuria. Clinical blood pressure (BP) and blood chemistry including plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were determined. Left ventricular mass index (LVMI) was also determined by echocardiography. Average BP was 129 ± 16/68 ± 10 mm Hg with the use of 2.0 antihypertensive drugs on average. Urinary salt excretion, PRA, and PAC were 8.1 ± 3.2 g/day, 2.2 ± 2.8 ng/mL/h, and 112 ± 54 pg/mL, respectively. Even in the patients taking angiotensin receptor blocker or angiotensin-converting enzyme inhibitors (n = 146), 15.1% showed low PRA (<0.5 ng/mL/h) levels and salt excretion in these patients with low PRA (9.1 ± 4.2 g/day) did not differ from those with higher PRA levels (8.2 ± 2.6 g/day, NS). There was no correlation between salt excretion and PRA (r = 0.03, NS), while salt excretion showed a significant negative correlation to PAC (r = −0.17, P < .05). Urinary salt excretion was also correlated with proteinuria (r = 0.25, P < .01) and LVMI (r = 0.16, P < .05). In the multivariate analysis, salt excretion contributed to proteinuria (P < .05) or LVMI (P = .11) independent of age, sex, serum creatinine, and BP levels. Results indicate that PRA levels were relatively low and unaffected by salt intake in Japanese patients treated with antihypertensive drugs. Since high salt intake was possibly associated with target organ damages, strict salt reduction should be encouraged.

Association of plasma renin activity and aldosterone–renin ratio with prevalence of chronic kidney disease

Although higher plasma renin activity (PRA) is associated with poor clinical outcomes including higher death and cardiovascular events, its association with prevalence of chronic kidney disease (CKD) is not clear. We hypothesized that higher levels of PRA and lower levels of aldosterone-to-PRA ratios (ARRs) are associated with greater CKD prevalence in a large and ethnically diverse population of southern California who underwent uniform healthcare. During the period 1 January 1998 to 31 October 2009, the adult population who was under the care of Kaiser Permanente Southern California with documented outpatient values of PRA and minimum of 6 months continuous enrollment were examined. CKD defined by an estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m2. PRA levels and ARR were categorized into quartiles. Multivariate logistic regressions were used to calculate odds ratios for CKD based on PRA controlling for age, sex, black race, diabetes status, hypertension, and type of medication use. We identified 9495 individuals including 7887 with hypertension. Study population included 60% women, 35% whites, 20% blacks, 20% Hispanics, and 26% diabetic patients. Adjusted odds ratios (95% confidence interval) for CKD across second, third, and fourth quartiles of PRA quartile (reference: first quartile) were 1.5 (1.2-1.7), 1.5 (1.3-1.8), and 2.2 (1.9-2.6), respectively. Each 10-unit increase in PRA was associated with odds ratio for CKD of 1.3 (1.2-1.4). ARR showed a similar but inverse trend with CKD. Higher levels of PRA are associated with greater rates of CKD in our large ethnically diverse population of primarily hypertensive patients. Whether modulation of PRA can mitigate prevalence of CKD needs to be studied in interventional trials.

Hemodynamic, Morphometric and Autonomic Patterns in Hypertensive Rats - Renin-Angiotensin System Modulation

BACKGROUND:Spontaneously hypertensive rats develop left ventricular hypertrophy, increased blood pressure and blood pressure variability, which are important determinants of heart damage, like the activation of renin-angiotensin system.AIMS:To investigate the effects of the time-course of hypertension over 1) hemodynamic and autonomic patterns (blood pressure; blood pressure variability; heart rate); 2) left ventricular hypertrophy; and 3) local and systemic Renin-angiotensin system of the spontaneously hypertensive rats.METHODS:Male spontaneously hypertensive rats were randomized into two groups: young (n=13) and adult (n=12). Hemodynamic signals (blood pressure, heart rate), blood pressure variability (BPV) and spectral analysis of the autonomic components of blood pressure were analyzed. LEFT ventricular hypertrophy was measured by the ratio of LV mass to body weight (mg/g), by myocyte diameter (μm) and by relative fibrosis area (RFA, %). ACE and ACE2 activities were measured by fluorometry (UF/min), and plasma renin activity (PRA) was assessed by a radioimmunoassay (ng/mL/h). Cardiac gene expressions of Agt, Ace and Ace2 were quantified by RT-PCR (AU).RESULTS:The time-course of hypertension in spontaneously hypertensive rats increased BPV and reduced the alpha index in adult spontaneously hypertensive rats. Adult rats showed increases in left ventricular hypertrophy and in RFA. Compared to young spontaneously hypertensive rats, adult spontaneously hypertensive rats had lower cardiac ACE and ACE2 activities, and high levels of PRA. No change was observed in gene expression of Renin-angiotensin system components.CONCLUSIONS:The observed autonomic dysfunction and modulation of Renin-angiotensin system activity are contributing factors to end-organ damage in hypertension and could be interacting. Our findings suggest that the management of hypertensive disease must start before blood pressure reaches the highest stable levels and the consequent established end-organ damage is reached.

Morbid Obesity, Hypertensive Disease and the Renin-Angiotensin-Aldosterone Axis

Resistance to insulin and secondary hyperinsulinemia seem to be the putative link between morbid obesity (MO) and hypertensive disease (HD). Adipose tissue can secrete leptin and angiotensinogen, among other substances. Leptin activates the sympathetic nervous system, leading to HD. Angiotensinogen is a substrate for renin, therefore taking part in the renin-angiotensin-aldosterone axis and the regulation of blood pressure. In MO, both hypertrophy and hyperplasia of the adipocytes lead to an increase in the secretion of both substances, leading to loss of the equilibrium between the levels of both hormones. The aim of the present study was to evaluate these abnormalities and their potential reversibility following bariatric surgery. Data from 100 patients with MO was retrospectively evaluated. Anthropometric data, the plasma renin activity (PRA), plasma levels of aldosterone, ACE, potassium and sodium were collected both prior to surgery and 6, 12, 24 and 36 months after surgery. The waist-hip ratio (WHR) before surgery allowed classification of our patients in two groups: central obesity (WHR > or =0.90 in men and > or =0.85 in women); peripheral obesity (WHR <0.90 in men and <0.85 in women). In patients with central obesity, high levels of PRA, aldosterone and ACE with sodium retention and potassium loss and high insulin levels, were found. These changes were not found in patients with peripheral obesity. After gastric bypass, these abnormalities tended to disappear, mainly in the first 6 months. The reduction of BMI and WHR after gastric bypass confirmed this operation to be effective against MO. The high basal levels of insulin and the high rate of HD and diabetes in patients with central obesity seem to indicate that they suffer a metabolic syndrome with significant hormonal imbalances and sodium retention. Patients with peripheral obesity only showed a peripheral resistance against insulin, probably with a shorter duration of the hormonal action, but they did not show hormonal abnormalities or sodium retention. After gastric bypass these abnormal hormone levels tended to normalize.

W05.155 The role of T-cadherin in cell adhesion and migration, interaction with LDL and signalling

The purpose of this study was to test the hypothesis that plasma renin activity (PRA) is a risk factor for cardiovascular disease. Four groups of New Zealand rabbits were used to study the effects of PRA and hypertension on atherogenesis. Control groups were fed normal rabbit chow (Group I), or normal chow supplemented with 0.25% cholesterol (Group III) Group II animals were fed normal chow, had a clip placed around the left renal artery and were contralaterally nephrectomized (one-kidney-one-clip, 1K-1C). The renal arteries and kidneys of Group IV animals, which were fed a cholesterol diet, were manipulated similarly. Blood pressure and blood chemistry measurements were performed periodically over a 7-month period. The blood pressure was unaffected by either diet; however, PRA and aldosterone levels were greatly reduced in the 1 K-1 C groups (Groups II and IV). No atheroma were observed in any of the animals consuming the normal diet (Groups I and II) despite sharply elevated blood pressure in the Group II animals. Medial hypertrophy of small muscular arteries was observed in several Group II animals. All of the animals fed the atherogenic diet showed extensive aortic atheromata. There was, however, a significantly smaller lesion index for the normotensive cholesterol-fed animals (Group III) than those with increased blood pressure (Group IV). Likewise, microscopic evaluation of the aorta, coronary arteries, renal arteries, and kidneys mirrored this difference in the vascular involvement between the animals of Groups III and IV. We conclude that neither relatively high nor low PRA levels affect the development of atherosclerosis or other cardiovascular lesions. However, hypertension with a concomitantly high cholesterol diet acts synergistically in exacerbating atherogenesis.

Association of −344/T/C aldosterone synthase polymorphism (CYP11B2) with left ventricular structure and humoral parameters in young normotensive men

Background: Aldosterone plays an important role in development of left ventricular (LV) hypertrophy and myocardial fibrosis. We assessed the influence of the T‐344C polymorphism of aldosterone synthase – the rate‐limiting enzyme in aldosterone biosynthesis – on the structure of the left ventricle in young normotensive men. Design and methods: The population included 113 normotensive mid‐European Caucasian men aged 18–40 years (mean 27 ± 5 years). The genotype was assessed using polymerase chain reaction with subsequent cleavage with restriction enzyme HAEIII (restriction fragment length polymorphism method) and visualization with ethidium bromide. Plasma renin activity (PRA) and plasma aldosterone were measured. All subjects were examined by echocardiography and LV mass was assessed by using M‐mode based ASE formula. Results: The distribution of the genotypes was TT 23%:TC 55%:CC 22%. There were no differences in blood pressure among the groups. Men with the TT genotype had significantly higher levels of PRA (2.7 ± 1.7 vs 1.8 ± 1.0 vs 1.8 ± 1.1 ng/ml/h, p < 0.01) and slightly higher plasma levels of aldosterone (113 ± 64 vs 93 ± 43 vs 87 ± 39 pg/ml, p = 0,12). In the whole population, LV mass index (LVMI) did not differ significantly among the genotypes (92 ± 16 vs 86 ± 18 vs 84 ± 16 g/m2, p = 0.20). In the population divided according to PRA, subjects with high renin had significantly higher LVMI in presence of the TT genotype (95 ± 17 vs 84 ± 16 vs 81 ± 15 g/m2, p < 0.05). Conclusions: In agreement with previous studies, we found that the TT genotype of T‐344C polymorphism of aldosterone synthase gene was associated with significantly higher levels of PRA in normotensive men. In subjects with high PRA, the TT genotype was associated with higher values of the LVMI.

Plasma renin activity and metabolic risk factors in essential hypertension

Elevated plasma renin activity (PRA) has been shown to be associated with enhanced cardiovascular morbidity. In small series of patients (pts), high PRA levels have been observed in subjects with clustering of classical risk factors. Aim of the present study was to investigate the relationshipS between PRA and plasma lipids, glucose (G), insulin (I) and uric acid (UA) in a population of essential hypertensives (EH). Records of 487 EH, either untreated or whose treatment with diuretics, betablockers or ACE-inhibitors had been withdrawn at least 4 weeks before, were reviewed for baseline PRA, total, LDL- and HDL-cholesterol, triglycerides, serum G and UA and plasma I. All pts were on controlled Na intake; they were grouped according to quartiles of PRA (ngAI/ml/h)(I quart., median 0.15, range 0.05-0.25; II quart., median 0.40, range 0.30-0.60; III quart., median 0.90, range 0.65-1.30; IV quart., median 2.1, range 1.35-6.75). Sex distribution, body mass index (BMI), systolic and diastolic blood pressure values and 24-hour urinary Na were similar across quartiles of PRA. The pts in the highest quartile were slightly but significantly younger than those in the lowest quartile (46±11 vs 53±11, P<0.01). There were no significant differences in plasma lipids and serum G, whereas plasma I was highest in the highest quartile (Table). HOMA-IR, an index of insulin resistance, was also significantly higher in the IV compared with the I quartile (2.50±2.12 vs 2.05±1.35, P=0.016), even after correction for age and BMI. Serum UA was also significantly higher in the highest compared with the lowest PRA quartile. We conclude that in middle-aged, nondiabetic EH moderately elevated PRA levels are not associated with an unfavourable plasma lipid pattern; however, insulin resistance and UA levels appear to increase with increasing PRA values.

Plasma renin activity in hemodialyzed patients during long-term follow-up

Plasma renin activity (PRA) and mean arterial pressure (MAP) were determined in 11 patients after the initiation of maintenance hemodialysis for 8 to 10 years. PRA increased significantly from 2.3 ± 0.5 to 6.5 ± 1.3 ng/mL/h, whereas MAP was lowered during follow-up, and there was a strong correlation between these two ( r = 0.88, P < 0.001). Immediately before initiating hemodialysis, PRA was negatively correlated with the increase in PRA ( r = 0.62, P < 0.05) and positively correlated with the reduction in MAP ( r = 0.65, P < 0.05). PRA was elevated and MAP was markedly reduced in patients whose PRA was relatively low immediately before initiating hemodialysis, whereas PRA tended to be reduced and MAP was unchanged in patients with higher levels of PRA. These data suggest that renin secretion continues even after disuse atrophy of the kidneys with almost complete deterioration of its excretory function.

Renal hypertensive angiopathy: Comparison between chronic NO suppression and DOCA-salt intoxication

NG-nitro-L-arginine methyl ester (L-NAME) and 11-desoxycorticosterone plus salt intake (DOCA-salt) hypertensive rat models were compared to study the possible involvement of model-specific factors in the development of renal angiopathy and left ventricular hypertrophy (LVH). Blood pressure was measured in L-NAME, DOCA-salt hypertensive, and control Wistar rats, and the lesions of nephroangiosclerosis and left ventricular hypertrophy were evaluated after 7 weeks. Arterial wall cyclic guanosine monophosphate, plasma renin activity (PRA), and renal renin storage were assessed in parallel. For the same level of hypertension in the two models, the renal arterial fibrinoid necrotic lesions were significantly more frequent in L-NAME than in DOCA-salt hypertensive rats. In DOCA-salt hypertensive rats, PRA was decreased and arterial cGMP increased compared to controls. In the L-NAME model, arterial cGMP decreased and PRA showed a bimodal distribution in this intermediate stage of hypertensive disease. LVH was observed in DOCA-salt rats and only in the L-NAME rats with a high level of PRA. There was a close correlation between the lesions of nephroangiosclerosis, left ventricular index, and plasma renin activity in L-NAME rats. We therefore suggest that the activation of the renin-angiotensin system participates specifically in the development of the second stage of hypertension during chronic blockade of NO synthase involving nephroangiosclerosis and LVH.

Plasma renin activity in chagasic patients with and without congestive heart failure

Chagasic patients with advanced heart disease have fluid retention-dependent symptoms. Since fluid retention is mostly dependent on the renin-angiotensin-aldosterone system, chagasic patients with congestion related symptoms should have activation of the renin-angiotension-aldosterone system. The purpose of this investigation was to determine the plasma renin activity baseline values of chagasic patients with and without congestive heart failure. Twenty-eight patients with positive serology for Chagas' disease were studied. Nineteen patients were asymptomatic (functional class I New York Heart Association) and nine were symptomatic (functional classes II–IV). Cardiac catheterization and ventricular cineangiography were performed on 20 patients. The symptomatic patients had significantly higher plasma renin activity levels (4.11 ± 1.03 ng/ml/h) than the asymptomatic patients (1.08 ± 0.11 ng/ml/h, P < 0.001) and the normal sedentary controls (1.65 ± 0.22 ng/ml/h, P < 0.05, mean ± S.E.). The plasma renin activity baseline values of the asymptomatic and symptomatic patients correlated directly with the baseline heart rate ( r=0.77, P < 0.0001). The symptomatic patients had larger ventricular volumes, moderately depressed ejection fractions and increased left ventricular end-diastolic pressures. The plasma renin activity baseline values also correlated directly with the left ventricular diastolic pressures ( r=0.70, P < 0.0006) and with the left ventricular diastolic ( r=0.66, P < 0.001) and systolic volumes ( r=0.67, P < 0.001). These results indicate that chagasic patients with fluid retention-dependent symptoms and hemodynamic evidence of left ventricular systolic dysfunction have activation of the renin-angiotensin-aldosterone system.

Dietary sodium restriction and the development of two-kidney, one-clip hypertension in young versus adult rats.

To determine the effects of moderate versus severe dietary sodium restriction on the development of 2-kidney, 1-clip (2K,1C) hypertension, young male Wistar rats were placed on diets containing 9, 26, or 101 (control) mumol sodium/g food. Three days later, a solid silver clip (i.d. 0.20 mm) was placed on the left renal artery and diets were continued up to 6 weeks. Adult rats received a 0.25-mm clip. In young clipped rats receiving the 101 mumol/g diet, blood pressure (BP), plasma renin activity (PRA), and BP response to captopril were increased as early as 1 week after clipping and increased further over time. Moderate sodium restriction (26 mumol sodium/g) led to only a slight delay in the development of hypertension; the levels of BP and PRA, the BP response to captopril, and the extent of cardiac hypertrophy achieved by 6 weeks were not different between the 2K, 1C rats receiving 26 or 101 mumol sodium/g. Sodium restriction to 9 mumol/g decreased rate of growth and completely prevented the rise in BP and in left ventricular weight. At 3 and 6 weeks the severely sodium-restricted rats had significantly higher PRA levels than the 2K, 1C control group. However, the BP response to captopril was attenuated relative to the other hypertensive groups. In adult rats, this level of sodium restriction had a small, but significant effect on body weight, but still prevented the increase in BP and in left ventricular weight. In conclusion, dietary sodium restriction can prevent the development of 2K,1C hypertension in both young and adult rats, but only if the restriction is severe. This effect may relate to a marked reduction in the pressor effectiveness of the renin-angiotensin system by low sodium intake per se or by associated metabolic or other changes.

Secondary aldosteronism documented by plasma renin and aldosterone circadian rhythm in subjects with kidney or heart transplantation.

The circadian rhythm (CR) of plasma renin activity (PRA), plasma aldosterone (PA), and plasma cortisol (PC) was investigated in 8 patients with kidney transplantation, and in 10 patients with heart transplantation. Ten clinically healthy subjects were studied as controls. The transplanted patients were all under cyclosporine treatment associated with prednisone (PDN). Time-qualified levels of PRA and PA were seen to be higher than normal in both groups of transplanted patients. The analysis of PRA and PA circadian rhythm provided evidence for a systematically higher level of within-day concentrations. The higher level of oscillation suggests the occurrence of a condition of hyperreninemic hyperaldosteronism. The higher levels of PRA and PA 24-h values show no periodicity. The finding suggests the abrogation of the rhythmic function for renin-aldosterone system. The disappearance of PRA-PA circadian rhythm seems to be attributable to a side effect of immunosuppressive therapy.

Renin-Dependency of Glycyrrhizin-Induced Pseudoaldosteronism.

A prospective study was carried out on 12 patients with chronic hepatitis who were taking 546 mg/day of glycyrrhizin for 4 weeks in order to identify the factors responsible for the development of hypertension and hypokalemia. In 5 patients, blood pressure increased and serum potassium decreased after the treatment (responders). In the remaining 7 patients, these values were unchanged (nonresponders). There were no significant differences in age, plasma aldosterone, the catecholamine concentrations or serum transaminases. The basal plasma renin activity (PRA) in the responders was more than 1.5 ng/m/h (2.5 +/- 0.3 ng/m/h), while that in the non-responders was less than 1.5 ng/m/h (0.7 +/- 0.1 ng/ml/h). Furthermore, a positive correlation between the basal RPA and the changes in blood pressure, and a negative correlation between the basal PRA and the changes in potassium were found. These results suggest that patients with higher PRA levels are more likely to develop hypertension and hypokalemia when treated with glycrrhizin.