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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolic acidosis has recently been observed in rat models of salt-sensitive genetic hypertension. To test the hypothesis that salt sensitivity in humans may be associated with abnormal acid-base homeostasis, we performed arterial blood gas analyses in young (20-31 years old) normotensive subjects (n = 40) who were placed on a low salt diet (20 mmol NaCl/day) for 2 weeks with either 200 mmol sodium chloride or placebo added to the low salt diet for 1 week each in a randomized, single-blind crossover order. Furthermore, a subset of the subjects (seven salt-sensitive and eight salt-resistant) received 200 mmol sodium/day as the citrate salt as a supplement to the low salt diet for a third week. During each regimen, blood pressure as well as arterial pH and bicarbonate levels were measured. Salt sensitivity was defined as a significant drop in mean arterial pressure greater than 3 mm Hg (mean of 30 readings taken during each diet, p less than 0.05) while the subject was on the low salt diet. According to this definition, 16 subjects were salt-sensitive and 24 salt-resistant. During the high sodium chloride regimen, arterial pH and bicarbonate levels were significantly lower in the salt-sensitive than in the salt-resistant group (p less than 0.0001). The increase in blood pressure caused by sodium chloride correlated inversely to the arterial pH (r = -0.57, p = 0.0002) and bicarbonate levels (r = -0.52, p = 0.0007) during the high salt diet. Sodium chloride increased mean arterial blood pressure in the salt-sensitive subjects; sodium citrate did not. Sodium citrate led to an increase in pH and bicarbonate levels in both groups. Our finding that a sodium chloride-induced rise in blood pressure is associated with lower arterial plasma pH and bicarbonate levels points to an abnormality in renal acid-base regulation in salt-sensitive subjects.
Hypertension 1990 Oct
PMID:Salt sensitivity in humans is associated with abnormal acid-base regulation. 221 Aug 8

A chronic magnesium deficiency may be one of the causes of lifestyle-related diseases such as hypertension and diabetes. Serum Mg2+ concentration is strictly controlled by the reabsorption pathway in the renal tubules, but little is known about how Mg2+ reabsorption is upregulated. We searched for food compounds which can increase the expression levels of Mg2+ transport carriers including transient receptor potential melastatin 6 (TRPM6) channel and cyclin M2 (CNNM2). Sodium citrate (SC) increased the mRNA levels of TRPM6 and CNNM2 in renal tubular epithelial NRK-52E cells. The SC-induced elevation of TRPM6 was inhibited by U0126, a mitogen-activated protein kinase kinase (MEK) inhibitor, but the CNNM2 was not. SC increased the levels of p-ERK1/2 and p-c-Fos, which were inhibited by U0126. SC induced alkalization of culture medium. Both SC and alkalization enhanced Mg2+ influx, which was inhibited by U0126 and introduction of TRPM6 siRNA. The reporter activity of TRPM6 was increased by SC and alkalization, which was suppressed by mutation in an AP-1-binding site. The SC-induced elevation of p-ERK1/2 and p-EGFR was inhibited by diphenylene iodonium, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, and erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. SC did not change the level of acetyl histone H3, but increased the association of c-Fos with the promoter region of TRPM6. These results suggest that SC increases TRPM6 expression and Mg2+ influx mediated by the activation of NADPH oxidase and an EGFR/ERK/c-Fos pathway in the renal tubules.
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PMID:Sodium Citrate Increases Expression and Flux of Mg2+ Transport Carriers Mediated by Activation of MEK/ERK/c-Fos Pathway in Renal Tubular Epithelial Cells. 3024 94