Natriuretic peptide fragments as possible biochemical markers of hypertension in the elderly.

AIMS: To study the relationship between C-type natriuretic peptide (NT-proCNP) and other natriuretic peptides, such as pro-atrial natriuretic peptide [proANP(1-98)] and N-terminal pro-brain natriuretic peptide (NT-proBNP), in the elderly, investigating also their correlation with other traditional clinical markers of the hypertensive condition. METHODS: NT-proCNP, NT-proBNP and proANP(1-98) were measured in 57 elderly patients. They were hypertensive patients (n = 36) and normotensive controls (n = 21). Their anthropometric parameters, including Winsor's index and total and high-density lipoprotein cholesterol, were determined. RESULTS: A diagnostic role of NT-proBNP in hypertensive patients was detected by a model of logistic regression, which gave a significant result [odds ratio (OR) 1.0115, P = 0.0184]. By this model the area (AUC) under the receiver-operating characteristic (ROC) curve was 0.69 ±â€Š0.071 (P = 0.0075). On the basis of the ROC curve, the calculated serum NT-proBNP cut-off for the prediction of hypertension was greater than 164 pmol/l - the value being provided with a sensitivity of 89% coupled with a specificity of 55%. NT-proCNP and proANP(1-98) did not predict the hypertensive condition, although significant correlations were detected with serum lipid profile and creatinine levels. CONCLUSIONS: By using the logistic regression analysis, NT-proBNP was identified as a significant predictor of hypertension, whereas NT-proCNP and proANP circulating levels were not shown to reliably predict the hypertensive condition. Further validation by means of larger cohort studies is undoubtedly needed to assess the use of all three peptides to increase the performance of a possible test for the prediction of the hypertensive condition in humans.

Effect of prolonged physical exercise on urinary proANP1-30 and proANP31-67.

Dynamic exercise strongly affects atrial natriuretic peptides (ANP), in particular the mature bioactive alphaANP and the proANP fragments, namely proANP1-98, proANP1-30 and proANP31-67. The proANPs influence kidney functions and their plasma levels increase after physical exercise. We measured urinary proANP1-30 and proANP31-67 levels before and at the end of physical exercise in 28 well-trained male cyclists. For the first time, the proANP1-30 and proANP31-67 urinary levels in athletes before and at the end of a prolonged agonistic bicycle race were measured. Urinary creatinine and total proteins were also measured. The urinary proANP31-67, creatinine and total protein levels were significantly higher at the end of exercise than before. In contrast, proANP1-30/protein and proANP31-67/protein ratios decreased after exercise. Even proANP1-30/creatinine and proANP31-67/creatinine ratios were lower after exercise. A significant correlation between proANP1-30 and proANP31-67 urinary levels at the end of exercise was found. The proANP31-67/creatinine ratio before and after exercise also showed a significant correlation. The variation of urinary proANP fragments confirmed their possible role in physical exercise. In particular, it could be interpreted as a response of the body or kidney to renal impairment occurring during exercise.

Effects of acute, heavy-resistance exercise on urinary peptide hormone excretion in humans.

To examine physical exercise-related changes in urinary excretion of protein/peptide hormones and to correlate modifications with the general increase in post-exercise proteinuria, urine C-peptide, insulin and insulin-like growth factor-I (IGF-I) and their plasma concentrations were measured. Plasma and urinary C-peptide, insulin and IGF-I before (Bex) and at the end (Eex) of physical exercise (a 2.5-hour competition, 102 km) were analysed in 20 young cyclists. At Eex compared with Bex, concentration of urinary C-peptide decreased slightly but significantly (21.3 +/- 2.7 vs. 13.5 +/- 1.7 nmol/l), but urinary insulin and urinary IGF-I concentrations significantly increased at Eex (92.5 +/- 4.2 vs. 131.4 +/- 15.7 pmol/l and 10.0 +/- 2.1 vs. 33.6 +/- 3.8 pmol/l, respectively). Plasma insulin and plasma C-peptide significantly decreased, whereas plasma IGF-I was unchanged. Urinary concentrations of total proteins and creatinine significantly increased. Both Eex urinary C-peptide/urinary protein and urinary C-peptide/urinary creatinine ratios were significantly reduced. The correlation between C-peptide and insulin in plasma was confirmed at Bex as well as Eex, but in urine only at Bex. An increased renal tubular reabsorption of C-peptide at the end of exercise might be suggested, but the expected values considering creatinine excretion were almost three times less. The Eex urinary insulin concentration was higher than expected, considering the circulation levels, but lower when compared with the expected concentration considering creatinine excretion. Physical exercise proteinuria, related to an increased protein filtration and a saturation of the mechanisms responsible for the reabsorption, does not appear similar for all peptide hormones.

Urinary insulin-like growth factor I in athletes, before and after physical exercise, and in sedentary subjects.

BACKGROUND: Insulin-like growth factor I (IGF-I), like growth hormone (GH), is excreted in urine in a smaller fraction than the concentration found in blood. Exercising subjects undergo post-exercise proteinuria. The present work aims to propose a method for urinary IGF-I analysis (uIGF-I) by defining urinary concentration in sedentary individuals and athletes before and after strenuous exercise. METHODS: Urine samples were collected from 30 sedentary healthy male individuals during the morning and from 30 well-trained cyclists, before and after a competition of about 3 h (150 km). uIGF-I was measured in undiluted acidified urine by radioimmunoassay (RIA) method using a purified polyclonal rabbit antibody, human 125I-IGF-I and a second anti-rabbit antiserum. The acidification of the urine samples and the excess of IGF-II addition in the incubation medium of the assay were used to dissociate the binding and to block the interference from IGF binding proteins (IGFBPs). Urinary growth hormone (uGH), total protein (utPr) and creatinine (ucr) concentrations were also measured by immunoradiometric assay (IRMA), colorimetric and capillary electrophoresis methods, respectively. RESULTS: The analysis range was 0-2500 ng/l (0-327 pmol/l), the intra- and inter-assay coefficients of variations (CVs) ranged from 2.3% to 7.8%, respectively. The detection limit was 0.6 pg/tube. The uIGF-I/creatinine (cr) ratio in healthy subjects was 70 +/- 8 pg/mg cr. The uIGF-I/creatinine ratio (pg/mg cr) was different (p<0.001) in athletes before vs. after competition 93 +/- 27 vs. 136 +/- 13. Athletes' [uIGF-I/total proteins] ratio (ng/mg tPr) before and post-exercise was 2.3 +/- 0.5 and 2.5 +/- 0.3, respectively. CONCLUSIONS: uIGF-I assay appears to be an effective way of monitoring IGF-I excretion. In the cyclists, in the pre-exercise state, uIGF-I was comparable with that measured in sedentary healthy individuals. In the cyclists, after strenuous exercise, the increased uIGF-I/cr and uGH/cr ratios suggested a relation with the post-exercise proteinuria. In conclusion, proteinuria physiologically obtained, such as post-exercise proteinuria, might be a new approach in IGF-I system investigation.