24-h Urinary Aldosterone Excretion Research Articles

Reference intervals for LC-MS /MS measurements of plasma renin activity, aldosterone, angiotensin II, and 24-hour urinary aldosterone in Northern Chinese Han population

BackgroundExamination of aldosterone to Renin Ratio (ARR) and plasma aldosterone concentration (PAC) or 24-h urinary aldosterone excretion (24-h UALD) was the necessary tests in confirmatory tests for primary aldosteronism (PA). We developed a combined liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for plasma renin activity (PRA), PAC, and angiotensin II (Ang II) and investigated their reference intervals (RIs) in northern Chinese Han population. The RIs of 24-h UALD excretion were also studied using LC-MS/MS. MethodsA total of 309 healthy volunteers were recruited in 3 cities in China. PRA, PAC, Ang II, and 24-h UALD were measured using the laboratory-developed LC-MS/MS. Multiple linear regression and the variance component model were applied to determine if the RI needed to be split. The RIs of PRA, PAC, and Ang II were determined using the nonparametric percentile method. ResultsThe laboratory-developed LC-MS/MS method was verified and showed good performance. Standard deviation ratio (SDR) sex for PAC and SDR region for Ang II are 0.466 and 0.407, respectively, indicating that the RIs of PAC and Ang II must be divided by sex and region, respectively. In addition, the SDR 24hUK for 24-h UALD is 0.579, indicating that the RI of 24-h UALD must be partitioned by urine potassium. ConclusionRIs were established for tests related to the renin-angiotensin-aldosterone system in the apparently healthy northern Chinese Han population by the LC-MS/MS method.

Hepatocellular carcinoma induces body mass loss in parallel with osmolyte and water retention in rats

AimsThe number of cancer survivors with cardiovascular disease is increasing. However, the effect of cancer on body fluid regulation remains to be clarified. In this study, we evaluated body osmolyte and water imbalance in rats with hepatocellular carcinoma. Main methodsWistar rats were administered diethylnitrosamine, a carcinogenic drug, to establish liver cancer. We analyzed tissue osmolyte and water content, and their associations with aldosterone secretion. Key findingsHepatocellular carcinoma rats had significantly reduced body mass and the amount of total body sodium, potassium, and water. However, these rats had significantly increased relative tissue sodium, potassium, and water content per tissue dry weight. Furthermore, these changes in sodium and water balance in hepatocellular carcinoma rats were significantly associated with increased 24-h urinary aldosterone excretion. Supplementation with 0.25% salt in drinking water improved body weight reduction associated with sodium and water retention in hepatocellular carcinoma rats, which was suppressed by treatment with spironolactone, a mineralocorticoid receptor antagonist. Additionally, the urea-driven water conservation system was activated in hepatocellular carcinoma rats. SignificanceThese findings suggest that hepatocellular carcinoma induces body mass loss in parallel with activation of the water conservation system including aldosterone secretion and urea accumulation to retain osmolyte and water. The osmolyte and water retention at the tissue level may be a causative factor for ascites and edema formation in liver failure rats.

A speckle tracking echocardiographic study on right ventricular function in primary aldosteronism.

We investigated right ventricular function using speckle tracking echocardiography (STE) in patients with primary aldosteronism. Our study included 51 primary aldosteronism patients and 50 age and sex-matched primary hypertensive patients. We performed two-dimensional echocardiography to measure cardiac structure and function. We performed STE offline analysis on right ventricular four-chamber (RV4CLS) and free wall longitudinal strains (RVFWLS). Primary aldosteronism patients, compared with primary hypertensive patients, had a significantly (P ≤ 0.045) greater left ventricular mass index (112.0 ± 22.6 vs. 95.8 ± 18.5 g/m) and left atrial volume index (26.9 ± 6.0 vs. 24.7 ± 5.6 ml/m) and higher prevalence of left ventricular concentric hypertrophy (35.3 vs. 12.0%), although they had similarly normal left ventricular ejection fraction (55-77%). Primary aldosteronism patients also had a significantly (P ≤ 0.047) larger right atrium and ventricle, lower tricuspid annular plane systolic excursion, and higher E/E't (the peak early filling velocity of trans-tricuspid flow to the peak early filling velocity of lateral tricuspid annulus ratio), estimated pulmonary arterial systolic pressure and right ventricular index of myocardial performance. On the right ventricular strain analysis, primary aldosteronism patients had a significantly (P < 0.001) lower RV4CLS (-18.1 ± 2.5 vs. -23.3 ± 3.4%) and RVFWLS (-21.7 ± 3.7 vs. -27.9 ± 4.5%) than primary hypertensive patients. Overall, RV4CLS and RVFWLS were significantly (r = -0.58 to -0.41, P < 0.001) correlated with plasma aldosterone concentration and 24-h urinary aldosterone excretion. After adjustment for confounding factors, the associations for RV4CLS and RVFWLS with 24-h urinary aldosterone excretion remained significant (P < 0.001), with a standardized coefficient of -0.48 and -0.55, respectively. In addition to left ventricular abnormalities, primary aldosteronism patients also show impaired right ventricular function, probably because of hyperaldosteronism.

Left atrial myocardial dysfunction in patients with primary aldosteronism as assessed by speckle-tracking echocardiography.

We investigated the left atrial myocardial deformation in patients with primary aldosteronism using the speckle-tracking echocardiographic (STE) strain imaging technique. Our study included 107 primary aldosteronism patients [52 aldosterone-producing adenoma (APA) and 55 idiopathic hyperaldosteronism (IHA)] and 50 primary hypertensive patients. We performed conventional echocardiography to measure left atrial volume and ejection fraction, and STE to estimate left atrial myocardial deformation including peak velocity, strain and strain rate and calculate the ratio of E/e' to left atrial strain during left ventricular systole as the left atrial stiffness index. Patients with APA, compared with those with IHA and primary hypertension had a significantly (P < 0.001) lower serum potassium concentration and higher 24-h urinary aldosterone excretion and plasma aldosterone-to-renin ratio. Patients with APA had a significantly (P < 0.01) larger maximal, precontraction, and minimal left atrial volumes and lower total, active and passive left atrial emptying fractions than those with IHA and primary hypertension. Among the three groups, patients with APA showed lowest left atrial velocity, strain, and strain rate during ventricular systole, early diastole and late diastole (P < 0.05) and highest left atrial stiffness index (P < 0.001). In unadjusted analysis, the left atrial strain, strain rate and stiffness index were significantly (P < 0.05) associated with plasma aldosterone concentration and urinary aldosterone excretion. After adjustment for various confounding factors, these associations remained statistically significant for urinary aldosterone excretion (P < 0.05) but not plasma aldosterone concentration (P ≥ 0.05). Patients with primary aldosteronism, especially APA, had impaired left atrial deformation mechanics and increased left atrial stiffness, providing a promising insight into early detection of subclinical left atrial dysfunction by strain echocardiography.

Primary Aldosteronism: Does Underlying Pathology Impact Clinical Presentation and Outcomes Following Unilateral Adrenalectomy?

Patients undergoing unilateral adrenalectomy for primary aldosteronism (PA) may have a solitary adenoma, unilateral hyperplasia, or multiple adenomas on final pathology. This study investigated whether the underlying pathological diagnosis was associated with differences in clinical presentation and postoperative outcomes. A retrospective cohort study of patients undergoing unilateral adrenalectomy for PA from 2004 to 2015 at our institution was performed. Baseline clinical and laboratory parameters, as well as postoperative biochemical and hypertension cure rates, were compared across the three aforementioned pathological groups. Of 206 patients who met criteria for inclusion, 152 (73.8%) had a single adenoma, 33 (16%) had unilateral hyperplasia, and 21 (10.2%) had multiple unilateral adenomas. Patients with unilateral hyperplasia were more likely to be male (81.2% vs 57.9%, P = .03), undergo left-sided adrenalectomy (78.8% vs 47.4%, P < .01), and had a lower median adrenal venous sampling lateralization index (9.8 vs 19.8, P = .04) compared to those with solitary, but not multiple unilateral adenomas. No differences were seen in age, duration of hypertension, preoperative plasma aldosterone levels, plasma renin activities, 24-h urinary aldosterone excretion, serum potassium concentrations, and the number of preoperative antihypertensive medications across all three pathological groups. All patients achieved biochemical cure following adrenalectomy, and no significant differences in the rates of hypertension cure or improvement were observed in comparisons across pathological subtype. Clinical presentation and postoperative outcomes are similar regardless of underlying pathology in patients with PA. Because one in four patients may harbor unilateral hyperplasia or multiple adenomas, total unilateral adrenalectomy should be performed as the operation of choice over adrenal-sparing approaches.

151. Aldosterone as independent predictor of placental and birth weights: Odense Child Cohort study

Introduction Aldosterone is involved in plasma volume expansion and its levels, along with the levels of other members of the renin-angiotensin-aldosterone system (RAAS), are increased in healthy pregnancy. Aldosterone appears to contribute to an optimal fetal development by enhancing placental growth factor (PlGF) expression and trophoblast cell proliferation. In contrast to normal pregnancy, aldosterone is suppressed in preeclampsia. Hypothesis Aldosterone independently contributes to placental and fetal growth. Methods The project is based on data from the Odense Child Cohort, a prospective population-based study from the Municipality of Odense, Denmark, currently with 2500 active families. The participants were recruited between 2010 and 2012. To analyze plasma aldosterone levels and urinary aldosterone excretion (UAldoV), we used a subsample of 637 urine samples (24-h collections) from gestational week 28. Plasma aldosterone and UAldoV were determined by a commercially available ELISA. Predictive values of aldosterone were assessed by multiple regression analysis. Primary outcomes were placental weight (PW) and gestational age-adjusted birth weight Z-score (BW sds). Results UAldoV, but not plasma aldosterone concentration, independently contributed to PW and BW sds (adjusted β coefficients ± SEM: 3.21 ± 1.51, p Discussion At 28 weeks of gestation, 24-h urinary aldosterone excretion was an independent predictor of placental and birth weights. In perspective, aldosterone could be a candidate biomarker for future screening and monitoring programs of high-risk pregnancies. Our findings support the physiological role for aldosterone and likely NaCl conservation for normal pregnancy. Mineralocorticoid supplementation could be considered for pregnancies with high risk for IUGR in order to achieve elevated levels of mineralocorticoids and thus benefit placental and fetal development.

Effects of continuous positive airway pressure treatment on aldosterone excretion in patients with obstructive sleep apnoea and resistant hypertension

Aldosterone excess has been equally associated with resistant hypertension (RHT) and obstructive sleep apnoea (OSA). We conducted a randomized controlled study to assess the effect of continuous positive airway pressure (CPAP) treatment on 24-h urinary aldosterone excretion in patients with RHT and moderate/severe OSA. A total of 117 patients were randomized (57 CPAP and 60 control groups). Aldosterone excretion was determined by 24 h urine (24h-UAldo) collected at randomization and after 6 months of follow-up. Twenty-four hour UAldo differences were assessed by general linear model with the allocation group (CPAP or control) as a fixed factor adjusted for their respective baseline values. Both intention-to-treat and per-protocol (45 patients with optimal adherence to CPAP) analyses were performed. Baseline 24h-UAldo was higher in severe OSA than in moderate OSA patients. After CPAP treatment, there was a borderline significant reduction in 24h-UAldo [mean difference: -2.5 μg/24 h; 95% confidence interval (95% CI): -5.3 to +0.3 μg/24 h; P = 0.07] in intention-to-treat analysis, whereas in the per-protocol analysis, the CPAP group had a greater reduction in 24h-UAldo than the control group (mean difference: -3.3 μg/24 h; 95% CI: -6.1 to -0.4 μg/24 h; P = 0.027). This effect occurred solely in patients with uncontrolled ambulatory BPs, and was more pronounced in those with the nondipping pattern, not using spironolactone, less obese, and with lowest sleep SaO2 levels. Only optimal CPAP treatment reduced aldosterone excretion in patients with uncontrolled RHT, while on intention-to-treat the effect was borderline. Although nondefinitive, our results suggest that CPAP treatment might improve cardiovascular outcomes by reducing aldosterone excess in resistant hypertensive individuals with OSA. ClinicalTrials.gov Identifier: NCT01508754.

Association of left ventricular mass with the AGTR1 A1166C polymorphism

The A1166C polymorphism is located within the microRNA-155 binding site of the human angiotensin II (Ang II) type-1 receptor (AGTR1) gene. The C allele interferes with the base-pairing complementariness between AGTR1 mRNA and microRNA-155 and thereby increases AGTR1 protein expression in vitro. We hypothesized that left ventricular (LV) mass is associated with the AGTR1 A1166C polymorphism. Among 708 individuals (mean age, 49.4 years; 51.8% women) randomly recruited in a white European population, we measured LV structure by two-dimensional guided M-mode echocardiography, the AGTR1 A1166C polymorphism and the 24-h urinary aldosterone. We applied a mixed model to assess phenotype-genotype associations while adjusting for covariables and accounting for relatedness. The AA (49.1%), AC (42.8%), and CC (8.1%) genotypes were in Hardy-Weinberg equilibrium. Using a recessive model, CC homozygotes compared to A-allele carriers showed significant increases (P < 0.021) in LV mass index (+5.78 ± 2.25 g/m(2)), mean wall thickness (MWT) (+0.48 ± 0.15 mm), interventricular septum (IVS) (+0.60 ± 0.18 mm) and posterior wall thickness (PWT) (+0.34 ± 0.15 mm), but lower 24-h urinary aldosterone excretion (geometric mean, 22.4 vs. 19.0 nmol; P = 0.050). Sensitivity analyses in 552 participants untreated for hypertension were confirmatory. LV mass index is associated with the AGTR1 A1166C polymorphism. Further research should clarify to what extent this association might be mediated via different expression of AGTR1 as modulated by microRNA-155.

Abstract 2464: Severity of Obstructive Sleep Apnea Dependent upon Aldosterone Status in Subjects with Resistant Hypertension

Background: Obstructive sleep apnea (OSA) and hyperaldosteronism are common in subjects with resistant hypertension. Prior results from our laboratory relate severity of OSA to aldosterone levels in patients with resistant hypertension suggesting that the 2 disease entities may be mechanistically linked. Objective: This study prospectively evaluated the relation between OSA severity and aldosterone status in subjects with resistant hypertension. Methods: One hundred nine consecutive subjects (age 55.9±9.3 years; 50% male) with resistant hypertension referred to a university clinic for resistant hypertension were prospectively evaluated with plasma renin activity (PRA), plasma aldosterone concentration, and 24-hr urinary aldosterone excretion. Hyperaldosteronism was defined as a PRA &lt;1.0 ng/mL/hr and 24-h urinary aldosterone excretion ≥ 12 μg/24-hr. Remaining patients were considered as having normal-aldosterone status. All subjects were evaluated by full-night attended diagnostic polysomnography. OSA was defined as an apnea-hypopnea index (AHI) ≥ 5 events/hr. Results : Hyperaldosteronism was present in 28% of subjects. Overall, OSA was diagnosed in 77% of subjects; 81% of the high-aldosterone and 74% of the normal-aldosterone subjects. In subjects with hyperaldosteronism, plasma aldosterone and urinary aldosterone excretion correlated with AHI (r = 0.723, p &lt;0.001 and r = 0.639, p &lt;0.001, respectively) but not in the normal-aldosterone subjects (r = 0.008, p = 0.94 and r = 0.042, p = 0.71 respectively). Atrial natriuretic peptide (ANP) levels were significantly higher in the high-aldosterone compared to normal-aldosterone subjects (89±57 vs. 67±102 pg/ml; p = 0.03). Conclusion: OSA is extraordinarily common in patients with resistant hypertension. A significant correlation between both plasma and urinary aldosterone levels and severity of OSA is observed in high-aldosterone but not normal-aldosterone subjects. The higher level of ANP in high-compared to normal-aldosterone subjects suggests greater intravascular fluid retention in the former subjects. These results suggest worsening of OSA in patients with hyperaldosteronism secondary to chronic aldosterone-induced intravascular fluid retention.

Aldosterone excess and resistance to 24-h blood pressure control

Aldosterone excess has been reported to be a common cause of resistant hypertension. To what degree this represents true treatment resistance is unknown. The present study aimed to compare the 24-h ambulatory blood pressure monitoring (ABPM) levels in resistant hypertensive patients with or without hyperaldosteronism. Two hundred and fifty-one patients with resistant hypertension were prospectively evaluated with an early-morning plasma renin activity (PRA), 24-h urinary aldosterone and sodium, and 24-h ABPM. Daytime, night-time, and 24-h blood pressure (BP) and nocturnal BP decline were determined. Hyperaldosteronism (H-Aldo) was defined as suppressed PRA (<1.0 ng/ml per h or <1.0 mug/l per h) and elevated 24-h urinary aldosterone excretion (>/= 12 mug/24-h or >/= 33.2 nmol/day) during ingestion of the patient's routine diet. In all patients, the mean office BP was 160.0 +/- 25.2/89.4 +/- 15.3 mmHg on an average of 4.2 medications. There was no difference in mean office BP between H-Aldo and normal aldosterone status (N-Aldo) patients. Daytime, night-time, and 24-h systolic and diastolic BP were significantly higher in H-Aldo compared to N-Aldo males. Daytime, night-time, and 24-h systolic BP were significantly higher in H-Aldo compared to N-Aldo females. Multivariate analysis indicated a significant interaction between age and aldosterone status such that the effects of aldosterone on ambulatory BP levels were more pronounced with increasing age. In spite of similar office BP, ABPM levels were higher in resistant hypertensive patients with H-Aldo. These results suggest that high aldosterone levels impart increased cardiovascular risk not reflected by office BP measurements.

Estimation of 24-h aldosterone secretion in the dog using the urine aldosterone:Creatinine ratio

Objectives One potential method of evaluating renin–angiotensin–aldosterone system (RAAS) activation involves the quantification of urinary aldosterone excretion. While blood concentrations of aldosterone are easily obtained, results may be misleading because of minute-to-minute variation in aldosterone secretion and subsequent blood concentrations. Urinary aldosterone concentration measurement represents a more consistent “pooled” index of aldosterone secretion, but obtaining 24-h urine samples is time-consuming, difficult, and fraught with potential error. We postulated that the urinary aldosterone:creatinine ratio, measured from spot urine samples, would correlate well with 24-h urinary aldosterone excretion, and would provide a simple index of aldosterone excretion that would eliminate the need for 24-h urine collection. Animals, materials and methods After validating an assay for aldosterone in canine urine, 24-h urinary aldosterone excretion was determined by radioimmunoassay from 8 normal, male beagle dogs under control conditions, after RAAS stimulation with amlodipine administration, and after RAAS attenuation with the addition of enalapril to amlodipine administration. Spot urine samples, each obtained at the same time of day, were used to determine the aldosterone:creatinine ratio during control conditions, RAAS stimulation, and RAAS attenuation. Results The aldosterone:creatinine ratio from spot-checked urine samples correlated well with 24-h urinary aldosterone excretion ( r = 0.77, P < 0.0001). Conclusions A spot urinary aldosterone:creatinine ratio might be substituted for 24-h urinary aldosterone determination.

Aldosterone Excretion Among Subjects With Resistant Hypertension and Symptoms of Sleep Apnea

The severity of obstructive sleep apnea (OSA) correlates with the difficulty of controlling BP. The mechanism, however, by which sleep apnea contributes to the development of resistant hypertension remains obscure. Having observed a high prevalence of OSA among hypertensive subjects with primary hyperaldosteronism, we hypothesized a possible association between sleep apnea and aldosterone excretion. In consecutive subjects referred to a university clinic for resistant hypertension, we prospectively determined plasma renin activity (PRA), plasma aldosterone concentration (PAC), and 24-h urinary aldosterone excretion during high dietary salt ingestion. In addition, all subjects completed the Berlin Questionnaire, a survey designed to identify subjects at risk of having sleep apnea. Primary hyperaldosteronism (PA) was defined as a PRA < 1.0 ng/mL/h and 24-h urinary aldosterone excretion > 12 micro g during high urinary sodium excretion (> 200 mEq/24 h). Of the 114 subjects evaluated, 72 subjects had a high probability and 42 subjects had a low probability of having sleep apnea based on their responses to the Berlin Questionnaire. Subjects at high risk for sleep apnea were almost two times more likely to have PA diagnosed (36 vs 19%, p < 0.05), tended to have lower PRA (1.2 +/- 1.8 ng/mL/h vs 1.9 +/- 4.1 ng/mL/h), and had significantly greater 24-h urinary aldosterone excretion (13.6 +/- 9.6 micro g vs 9.8 +/- 7.6 micro g, p < 0.05) compared to subjects at low risk of sleep apnea. These data provide evidence of increased aldosterone excretion in subjects with resistant hypertension and symptoms of sleep apnea. While the causality of this association is unknown, it is hypothesized that sleep apnea contributes to the development of resistant hypertension by stimulating aldosterone excretion.

Role of dietary potassium in the hyperaldosteronism and hypertension of the remnant kidney model.

The remnant kidney model of progressive renal disease is marked by arterial hypertension, especially when produced by nephrectomy and partial infarction. Hyperaldosteronism sustains much of the hypertension, but the stimuli to the increased aldosterone levels are uncertain. It is hypothesized that the hyperaldosteronism attending this model stems from the combination of fixed dietary potassium load in the face of reduced filtration on the one hand, and persistent renin secretion from the scarred remnant kidney on the other. This hypothesis predicted that dietary potassium restriction would lower aldosterone and BP in this model. To test this prediction, two groups of rats with a remnant kidney were studied. Group 1 consumed 0.4 +/- 0.06 mEq (mean +/- SD) of potassium chloride daily, and group 2 ate 4.8 +/- 1.0 mEq daily. Two sham-operated groups with intact kidneys also were studied. Group 3 consumed 1.7 +/- 0.2 mEq daily and group 4 ate 15.2 +/- 1.4 mEq daily. These levels of intake were designed to provide at least as much potassium per liter of GFR in the sham groups as in the remnant kidney rats. Systolic BP (SBP), 24-h protein excretion, plasma aldosterone levels, 24-h urinary aldosterone excretion, and plasma renin activity (PRA) were determined in all groups at 2 wk. At 4 wk, after SBP and protein excretion measurements, remnant kidneys were perfusion-fixed for morphometric analysis. SBP was normal in both sham-operated groups and was not different between the groups (113 +/- 13 versus 117 +/- 2 mmHg, group 3 versus group 4). In the remnant animals, SBP at 2 wk followed potassium intake: Group 1 had a lower SBP than group 2 (140 +/- 26 versus 170 +/- 34 mmHg, P = 0.005). The same SBP pattern persisted at 4 wk (153 +/- 25 versus 197 +/- 27 mmHg, group 1 versus group 2, P = 0.0006). However, 24-h urinary protein excretion was not different between the two groups with remnant kidneys at either 2 or 4 wk. Both plasma and 24-h urinary aldosterone excretion at 2 wk followed potassium intake (120 +/- 124 versus 580 +/- 442 pg/ml for plasma aldosterone, group 1 versus group 2, P = 0.03, and 2.6 +/- 1.8 versus 23.2 +/-9.8 ng/d for urinary aldosterone, group 1 versus group 2, P = 0.0001). PRA, however, followed a reverse pattern in which dietary potassium restriction resulted in higher levels (16 +/- 6 versus 6 +/- 3 ng angiotensin I/ml per h, group 1 versus group 2, P = 0.01). A similar pattern for PRA and aldosterone excretion was also observed in the sham groups, in which lower potassium intake also resulted in a significantly higher PRA and lower aldosterone excretion. The constancy of BP in the sham groups likely reflects their lack of nephron reduction and greater sodium excretory capacity. Morphometric analysis in remnant animals revealed no significant difference between the two dietary groups in the prevalence of glomerular sclerosis, glomerular volume, or interstitial volume. It is concluded that dietary potassium is a potent determinant of hypertension in the remnant kidney model probably through the actions of aldosterone and that the high aldosterone secretion in this model is a function of the dietary potassium load. In this model, reduction in nephron number is also critical in promoting hypertension in conjunction with hyperaldosteronism.

Left ventricular filling profiles and angiotensin system activity in elite baseball players

Left ventricular (LV) filling profiles in elite baseball players has not been reported in the literature. Also, angiotensin system activity in athletes has never been reported. We used echocardiography to compare 20 male elite baseball players (aged 21.9±1.0 years) with those of age- and sex-matched healthy sedentary subjects. Compared with the normal group, the athlete group showed a significant increase in LV mass, LV diastolic and systolic dimension, and left atrial dimension ( P<0.05, <0.001, <0.001, and <0.001, respectively). No differences in relative wall thickness or fractional shortening were found between these two groups. Diastolic filling profiles, including peak early diastolic filling velocity ( E), peak late diastolic filling velocity ( A), E: A ratio, early time–velocity integral ( E i), atrial time–velocity integral ( A i), E i: A i ratio, early filling time, deceleration time of early filling, and isovolumic relaxation time, were similar in both groups. Angiotensin system activity, including plasma renin activity, plasma aldosterone, and 24-h urinary aldosterone excretion, showed no difference between these two groups. Conclusion: This study suggests that normal LV filling profile, which is mediated partly by normal angiotensin system activity, is not related to increase in LV dimension and mass in elite baseball players.

Comparison of the Angiotensin II Antagonist UP269–6 with the Angiotensin Converting Enzyme Inhibitor Enalapril in Normotensive Volunteers Challenged with Angiotensin I

We assessed the inhibitory effect of UP269-6, a new orally active angiotensin II (ANG II) receptor antagonist, on the pressor action of exogenous ANG I in healthy male volunteers maintained on an unrestricted sodium intake and compared it with that of enalapril. Seven different single doses of UP269-6 ranging from 5 to 180 mg, 20 mg enalapril, or placebo were administered to 16 subjects in a double-blind fashion. The order of placebo and enalapril was randomized, and UP269-6 was given in an ascending dose order. The peak systolic blood pressure (SBP) response to a test dose of ANG I was determined serially before and after oral drug administration by monitoring finger BP by a photoplethysmographic method. No drug-related side effect was observed. There was a dose-dependent inhibition of the SBP response to the ANG I challenge. Doses as low as 40 to 80 mg had blocking effects quite similar to that of enalapril 20 mg. Ten hours after the 20- and 40-mg doses of UP269-6, the SBP response was still attenuated when drug levels no longer were measurable in plasma. UP269-6 also produced a dose-related increase in active renin and ANG II levels at 24 h after drug intake. In these volunteers on unrestricted salt intake, no statistically significant effect on 24-h urinary aldosterone excretion was observed. Based on these preliminary data, the pharmacokinetic drug half-life (t 1/2) was estimated at 4.7 h and the EC50 was estimated at 41 ng/ml. UP269-6 appears to be a well-tolerated, potent, orally active, antagonist of ANG II receptors in men. Doses of 40-80 mg might block the ANG I pressor response as does enalapril 20 mg.