Is too much salt harmful? Yes.

The contribution of high sodium intake to hypertension and to the severity of immune-mediated diseases is still being heatedly debated in medical literature and in the lay media. This review aims to demonstrate two conflicting views on the topic, with the first part citing the detrimental effects of excessive salt consumption. Sodium plays a central role in volume and blood pressure homeostasis, and the positive correlation between sodium intake and blood pressure has been extensively researched. Despite the fact that the average of global daily salt consumption exceeds recommendations of international associations, health damage from excessive salt intake is still controversial. Individual differences in salt sensitivity are in great part attributed to this contradiction. Patients suffering from certain diseases as well as other vulnerable groups-either minors or individuals of full age-exhibit more pronounced blood pressure reduction when consuming a low-sodium diet. Furthermore, findings from the last two decades give insight into the concept of extrarenal sodium storage; however, the long-term consequences of this phenomenon are lesser known. Evidence of the relationship between sodium and autoimmune diseases are cited in the review, too. Nevertheless, further clinical trials are needed to clarify their interplay. In conclusion, for salt-sensitive risk groups in the population, even stricter limits of sodium consumption should be set than for young, healthy individuals. Therefore, the question raised in the title should be rephrased as follows: "how much salt is harmful" and "for whom is elevated salt intake harmful?"

Sex differences in renin response and changes of capillary diameters after renal ischemia/reperfusion injury.

Activation of the RAS has a crucial role in the progression of ischemia/reperfusion-associated CAD. The regulation of RAS differs in the two genders. However, the extent of gender differences and locations of renin production have not been revealed yet. We investigated in vivo the local renin production in the two genders during ischemia/reperfusion injury. In male and female Wistar rats, renal ischemia was induced followed by a reperfusion period of two, eight, 16, 24, or 48 h. We applied flow cytometry to measure renin content and multiphoton imaging to visualize renin granules and changes of peritubular diameters in vivo during ischemia/reperfusion. Renin content decreased in CD in the first eight h of reperfusion; however, after 16 h, its amount increased. In males, the production of renin was more pronounced, and the duration of vasoconstriction was longer with a subsequent phase of vessel hyperdilation compared to females. Renal ischemia/reperfusion injury induces renin response not only in the JGA, but also in the CD segment. Renin production is more explicit in males than in females which, via increased angiotensin II production, might explain the different dynamism of renal vessel regulation between the two genders.

Cyclooxygenase-2 Modulates Glycosaminoglycan Production in the Skin During Salt Overload.

Sodium (Na+) can accumulate in the skin tissue, sequestered by negatively charged glycosaminoglycans (GAGs). During dietary salt overload, the amount and charge density of dermal GAG molecules - e.g., hyaluronic acid (HA) and chondroitin sulfate (CS) - increases; however, the regulation of the process is unknown. Previously, it has been demonstrated that the level of cyclooxygenase-2 (COX-2) activity and the content of prostaglandin E2 (PGE2) are elevated in the skin due to high-salt consumption. A link between the COX-2/PGE2 system and GAG synthesis was also suggested. We hypothesized that in dermal fibroblasts (DFs) high-sodium concentration activates the COX-2/PGE2 pathway and also that PGE2 increases the production of HA. Our further aim was to demonstrate that the elevation of the GAG content is ceased by COX-2 inhibition in a salt overloaded animal model. For this, we investigated the messenger RNA (mRNA) expression of COX-2 and HA synthase 2 enzymes as well as the PGE2 and HA production of DFs by real-time reverse transcription PCR (qRT-PCR) and ELISA, respectively. The results showed that both high-sodium concentration and PGE2 treatment increases HA content of the media. Sodium excess activates the COX-2/PGE2 pathway in DFs, and COX-2 inhibition decreases the synthesis of HA. In the animal experiment, the HA- and CS disaccharide content in the skin of male Wistar rats was measured using high performance liquid chromatography-mass spectrometry (HPLC-MS). In the skin of rats receiving high-salt diet, the content of both HA- and monosulfated-CS disaccharides increased, whereas COX-2 inhibition blocked this overproduction. In conclusion, high-salt environment could induce GAG production of DFs in a COX-2/PGE2-dependent manner. Moreover, the COX-2 inhibition resulted in a decreased skin GAG content of the salt overloaded rats. These data revealed a new DF-mediated regulation of GAG synthesis in the skin during salt overload.

[The immunomodulatory role of sodium]. / A nátrium immunmoduláns szerepe.

High salt intake, which is common in the Western world, is the cause of several lifestyle diseases. Recent investigations shed light on novel extrarenal processes, which play role in the maintenance of sodium balance. In the short term, sodium storage of the skin may serve as a buffer against volume overload arising from the osmotic properties of sodium. Increased tissue sodium concentration may also potentiate immune response against infections. In the long run, however, tissue sodium concentration over a certain limit may initiate pathophysiological processes by provoking inflammatory response. Due to the immune modulating role of sodium, the effector cells of the innate as well as the adaptive immune system are activated, while certain regulator cells of the same systems are repressed, ultimately resulting in a proinflammatory state characterized by the imbalance of the immune system. Experiments applying dietary salt overload/salt depletion imply the role of sodium in the initiation/exacerbation of several diseases. Thus the relationship between sodium and the immune system may give an explanation to the pathomechanism of diseases with so far unknown origin such as hypertonia (primary, salt sensitive) or autoimmune diseases - all these putting tremendous pressure on the healthcare system due to their increasing incidence. Orv Hetil. 2019; 160(17): 646-653.