Amino Acid Metabolites of Dietary Salt Effects on Blood Pressure in Rat Urine and Kidney Tissue (part XI)
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ABSTRACT:
ORGANISM(S): Rattus Norvegicus
TISSUE(S): Kidney
DISEASE(S): Heart Disease
PROVIDER: ST000638 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
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Project description:BackgroundData are available that indicate an independent inverse relationship of dietary vegetable protein to the blood pressure (BP) of individuals. Here, we assess whether BP is associated with glutamic acid intake (the predominant dietary amino acid, especially in vegetable protein) and with each of 4 other amino acids that are relatively higher in vegetable than animal protein (proline, phenylalanine, serine, and cystine).Methods and resultsThis was a cross-sectional epidemiological study with 4680 persons 40 to 59 years of age from 17 random population samples in China, Japan, the United Kingdom, and the United States. BP was measured 8 times at 4 visits; dietary data (83 nutrients, 18 amino acids) were obtained from 4 standardized, multipass, 24-hour dietary recalls and 2 timed 24-hour urine collections. Dietary glutamic acid (percentage of total protein intake) was inversely related to BP. Across multivariate regression models (model 1, which controlled for age, gender, and sample, through model 5, which controlled for 16 possible nonnutrient and nutrient confounders), estimated average BP differences associated with a glutamic acid intake that was higher by 4.72% of total dietary protein (2 SD) were -1.5 to -3.0 mm Hg systolic and -1.0 to -1.6 mm Hg diastolic (z scores -2.15 to -5.11). Results were similar for the glutamic acid-BP relationship with each of the other amino acids also in the model; eg, with control for 15 variables plus proline, systolic/diastolic pressure differences were -2.7/-2.0 mm Hg (z scores -2.51, -2.82). In these 2-amino acid models, higher intake (by 2 SD) of each of the other amino acids was associated with small BP differences and z scores.ConclusionsDietary glutamic acid may have independent BP-lowering effects, which may contribute to the inverse relation of vegetable protein to BP.
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Project description:The aim of this study was to estimate the effects of dietary salt reduction on blood pressure (BP) in Chinese adults and the effects of China-specific cooking salt-reduction strategies (the use of salt substitutes and salt-restriction spoons). The PubMed and China National Knowledge Infrastructure databases were searched for studies satisfying the search criteria. Outcomes extracted from each included study were 24-h urinary sodium excretion, salt (sodium chloride) intake, and BP before and after dietary salt lowering. A random-effects meta-analysis was performed, and results were evaluated for evidence of publication bias and heterogeneity. Because most studies aggregated results for hypertensive and normotensive participants, estimates were made for hypertensive participants only and for hypertensive and normotensive participants combined. Six salt-restriction experiment studies (3,153 participants), 4 cooking salt-restriction spoon studies (3,715 participants), and 4 cooking salt-substitute studies (1,730 participants) were analyzed. In salt-restriction experiment studies, the pooled estimate of mean change in 24-h urinary sodium excretion in hypertensive participants was -163.0 mmol/day (95% confidence interval [CI]: -233.5 to -92.5 mmol/day), which was associated with a mean reduction of -8.9 mm Hg (95% CI: -14.1 to -3.7 mm Hg) in systolic BP. Each 1.00-g dietary salt reduction in hypertensive participants was associated with a reduction of 0.94 mm Hg in systolic BP (95% CI: 0.69 to 1.03 mm Hg). These systolic BP reductions in hypertensive participants were 1.71 times greater compared with the mixed hypertensive and normotensive group. Salt-restriction spoon studies demonstrated a 1.46-g decrease in daily salt intake level. The effect of salt-substitute use on systolic BP control was substantial among the hypertensive participants (-4.2 mm Hg; 95% CI: -7.0 to -1.3 mm Hg), but the change did not reach statistical significance in hypertensive and normotensive participants combined (-2.31 mm Hg; 95% CI: -5.57 to 0.94 mm Hg). Salt restriction lowers mean BP in Chinese adults, with the strongest effect among hypertensive participants. Future studies of salt-restriction strategies should be report results stratified by hypertension status and adjust for medication use.
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Project description:Uromodulin, also named Tamm Horsfall protein, have been associated with renal function and sodium homeostasis regulation. The authors sought to examine the effects of salt intake on plasma and urinary uromodulin levels and the association of its genetic variants with salt sensitivity in Chinese adults. Eighty patients from our natural population cohort were maintained sequentially either on a usual diet for 3 days, a low-salt diet (3.0 g) for 7 days, and a high-salt diet (18.0 g) for an additional 7 days. In addition, the authors studied 514 patients of the Baoji Salt-Sensitive Study, recruited from 124 families who received the same salt intake intervention, and investigated the association of genetic variations in uromodulin gene with salt sensitivity. Plasma uromodulin levels were significantly lower on a high-salt diet than on a baseline diet (28.3 ± 4.5 vs. 54.9 ± 8.8 ng/ml). Daily urinary excretions of uromodulin were significantly decreased on a high-salt diet than on a low-salt diet (28.7 ± 6.7 vs. 157.2 ± 21.7 ng/ml). SNPs rs7193058 and rs4997081 were associated with the diastolic blood pressure (DBP), mean arterial pressure (MAP) responses to the high-salt diet. In addition, several SNPs in the uromodulin gene were significantly associated with pulse pressure (PP) response to the low-salt intervention. This study shows that dietary salt intake affects plasma and urinary uromodulin levels and that uromodulin may play a role in the pathophysiological process of salt sensitivity in the Chinese populations.
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Project description:Available data indicate that dietary sodium (as salt) relates directly to blood pressure (BP). Most of these findings are from studies lacking dietary data; hence, it is unclear whether this sodium-BP relationship is modulated by other dietary factors. With control for multiple nondietary factors, but not body mass index, there were direct relations to BP of 24-hour urinary sodium excretion and the urinary sodium/potassium ratio among 4680 men and women 40 to 59 years of age (17 population samples in China, Japan, United Kingdom, and United States) in the INTERMAP (International Study on Macro/Micronutrients and Blood Pressure), and among its 2195 American participants, for example, 2 SD higher 24-hour urinary sodium excretion (118.7 mmol) associated with systolic BP 3.7 mm Hg higher. These sodium-BP relations persisted with control for 13 macronutrients, 12 vitamins, 7 minerals, and 18 amino acids, for both sex, older and younger, blacks, Hispanics, whites, and socioeconomic strata. With control for body mass index, sodium-BP-but not sodium/potassium-BP-relations were attenuated. Normal weight and obese participants manifested significant positive relations to BP of urinary sodium; relations were weaker for overweight people. At lower but not higher levels of 24-hour sodium excretion, potassium intake blunted the sodium-BP relation. The adverse association of dietary sodium with BP is minimally attenuated by other dietary constituents; these findings underscore the importance of reducing salt intake for the prevention and control of prehypertension and hypertension.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00005271.
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Project description:We examined the association between genetic risk score (GRS) for blood pressure (BP), based on single nucleotide polymorphisms identified in previous BP genome-wide association study meta-analyses, and salt and potassium sensitivity of BP among participants of the GenSalt study (Genetic Epidemiology Network of Salt Sensitivity). The GenSalt study was conducted among 1906 participants who underwent a 7-day low-sodium (51.3 mmol sodium/d), 7-day high-sodium (307.8 mmol sodium/d), and 7-day high-sodium plus potassium (60 mmol potassium/d) intervention. BP was measured 9× at baseline and at the end of each intervention period using a random zero sphygmomanometer. Associations between systolic BP (SBP), diastolic BP, and mean arterial pressure GRS and respective SBP, diastolic BP, and mean arterial pressure responses to the dietary interventions were assessed using mixed linear regression models that accounted for familial dependencies and adjusted for age, sex, field center, body mass index, and baseline BP. As expected, baseline SBP, diastolic BP, and mean arterial pressure significantly increased per quartile increase in GRS (P=2.7×10-8, 9.8×10-8, and 6.4×10-6, respectively). In contrast, increasing GRS quartile conferred smaller SBP, diastolic BP, and mean arterial pressure responses to the low-sodium intervention (P=1.4×10-3, 0.02, and 0.06, respectively) and smaller SBP responses to the high-sodium and potassium interventions (P=0.10 and 0.05). In addition, overall findings were similar when examining GRS as a continuous measure. Contrary to our initial hypothesis, we identified an inverse relationship between BP GRS and salt and potassium sensitivity of BP. These data may provide novel implications on the relationship between BP responses to dietary sodium and potassium and hypertension.
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