A High Salt Diet Alters Pressure-Induced Mechanical Activity of the Rat Lymphatics with Enhancement of Myogenic Characteristics

Mizuno, Risuke; Isshiki, Masashi; Ono, Nobuyuki; Nishimoto, Mitsuhiro; Fujita, Toshiro

doi:10.1089/lrb.2014.0028

Cited by 11 publications

(8 citation statements)

References 26 publications

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“…Data obtained in the present experiments provide a first detailed description of the acute effect of changes in osmolarity of extracellular tissue on the intrinsic contractility of collecting lymphatic vessels and on the possible interplay between a pure osmotic phenomenon, due to non-polar osmotic agents, and a superimposed ionic-mediated counterpart exerted by sodium and chloride ions, the most abundant ions of the extracellular fluids (Terry, 1994 ) and the ones more subjected to variations induced by diet and other phenomena (Mizuno et al, 2015a , b ).…”

Section: Discussionmentioning

confidence: 99%

“…This phenomenon has to be taken into account especially when large portions of the lymphatic vasculature are exposed for periods longer than 10–15 min to altered osmotic environments, since in these circumstances the control of interstitial or serosal volume might be greatly impaired by the lesser, or in the worst-case null, lymphatic drainage. Indeed, literature offers several reports that describe the eventual role played by the lymphatic vasculature in the dermis of high-salt diet fed rats (Mizuno et al, 2015a ) and hypertensive humans (Liu et al, 2011 ). Moreover, the response of lymphatic vessels to osmolarity might be pivotal in shaping the water and solute transport from the intestine (Lee, 1969 ) and in determining the bioavailability of drugs administered subcutaneously (Fathallah et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

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Fluid Osmolarity Acutely and Differentially Modulates Lymphatic Vessels Intrinsic Contractions and Lymph Flow

et al. 2018

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Lymph formation and propulsion rely on an extrinsic mechanism based on the forces that surrounding tissues exert upon the vessel wall and lumen and an intrinsic mechanism based on spontaneous, rhythmic contractions of the lymphatic muscle layer of collecting vessels. The two spontaneous pacemakers described in literature involve chloride-dependent depolarizations (STDs) and If-like currents, both giving rise to a variable contraction frequency (fc) of lymphatic vessels functional units (lymphangions). Several stimuli have been shown to modulate fc, such as temperature, shear stress, and several tissue chemical modulators (prostaglandins, norepinephrine, acetylcholine, substance P, and others). However, no detailed description is present in literature on the acute modulation of fc by means of osmolarity change of the surrounding interstitial space. Using a well-developed ex-vivo rat diaphragmatic preparation, in which osmolarity was changed by varying the concentration of D-mannitol in the perfusing solution and in later experiments the concentration of NaCl and then of Na+ and Cl− ions separately by ionic substitution, we provide detailed experimental evidences that a stepwise increase in osmolarity from control value (308 mOsm) up to 324 mOsm caused a reduction of fc down to ~-70% within the first 14 min, and that a stepwise decrease in osmolarity up to 290 mOsm induced an early fc increase to ~+34% of control, followed by a decline to an fc of ~-18% of control value. These variations were more dramatic when the same osmolarity changes were obtained by varying NaCl and/or Na+ or Cl− ions concentration, which caused an almost complete arrest of spontaneous contractility within 14 min from the application. Diastolic and systolic diameters and stroke volume were not affected by osmolarity changes, so that modulation of lymph flow closely followed that of fc. Modulation of lymph flow secondary to osmolarity changes is relevant if one considers that interstitial fluid balance is also dependent upon lymph drainage, and thus it is possible that, at least in the acute phase following variations of interstitial fluid osmolarity, its volume control might eventually be impaired due to the reduced or in the worst scenario null lymph drainage.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Fluid Osmolarity Acutely and Differentially Modulates Lymphatic Vessels Intrinsic Contractions and Lymph Flow

et al. 2018

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“…Kwon et al have, however, assessed lymphatic contractile function in rats and mice on high‐salt diet and were able to show dilated vessels having an increased contractility in the high‐salt diet animals. These observations were supported by data from isolated vessels showing an increased contractility during high‐salt conditions, but were complicated by data from the same researchers showing that there was a differential effect of high salt on afferent (reduced) and efferent (enhanced) collecting vessel contractility that make it hard to decide the net effect of high salt on lymph flow. Whether the lymphatics formed by lymphangiogenesis are capable of transporting increased electrolyte loads back to the general circulation and thereby to the kidney for final disposal that might be reflected as an increased lymph flow has yet to be determined (Figure ).…”

Section: Role Of Lymphatic Vessels and Innate Immune Cells In Salt Hamentioning

confidence: 93%

The interstitium conducts extrarenal storage of sodium and represents a third compartment essential for extracellular volume and blood pressure homeostasis

2017

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The role of salt in the pathogenesis of arterial hypertension is not well understood. According to the current understanding, the central mechanism for blood pressure (BP) regulation relies on classical studies linking BP and Na balance, placing the kidney at the very centre of long-term BP regulation. To maintain BP homeostasis, the effective circulating fluid volume and thereby body Na content has to be maintained within very narrow limits. From recent work in humans and rats, the notion has emerged that Na could be stored somewhere in the body without commensurate water retention to buffer free extracellular Na and that previously unidentified extrarenal, tissue-specific regulatory mechanisms are operative regulating the release and storage of Na from a kidney-independent reservoir. Moreover, immune cells from the mononuclear phagocyte system not only function as local on-site sensors of interstitial electrolyte concentration, but also, together with lymphatics, act as systemic regulators of body fluid volume and BP. These studies have established new and unexpected targets in studies of BP control and thus the pathophysiology of hypertension: the interstitium/extracellular matrix of the skin, its inherent interstitial fluid and the lymphatic vasculature forming a vessel network in the interstitium. Aspects of the interstitium in relation to Na balance and hypertension are the focus of this review. Taken together, observations of salt storage in the skin to buffer free extracellular Na and macrophage modulation of the extracellular matrix and lymphatics suggest that electrolyte homeostasis in the body cannot be achieved by renal excretion alone, but also relies on extrarenal regulatory mechanisms.

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“…17 How the lymphatic system influences BP is not fully uncovered. HSD-induced lymphatic changes are not only anatomic but also functional, as shown by increased lymphatic flow 18 and enhanced myogenic activity of isolated lymphatic vessels 19 in HSD-fed rats. Clearance of tissue water and electrolytes might play a role, enabling lowering of skin sodium content to preserve the availability for sodium storage and/or to preserve endothelial function (high sodium content was shown to increase vasoconstriction of blood vessels in rat models 20 ).…”

Section: Discussionmentioning

confidence: 99%

Salt-sensitive blood pressure rise in type 1 diabetes patients is accompanied by disturbed skin macrophage influx and lymphatic dilation—a proof-of-concept study

Wenstedt

Engberink

Rorije

et al. 2020

Translational Research

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Type 1 diabetes patients are more prone to have hypertension than healthy individuals, possibly mediated by increased blood pressure (BP) sensitivity to high salt intake. The classical concept proposes that the kidney is central in salt-mediated BP rises, by insufficient renal sodium excretion leading to extracellular fluid volume expansion. Recent animal-derived findings, however, propose a causal role for disturbance of macrophage-mediated lymphangiogenesis. Its relevance for humans, specifically type 1 diabetes patients, is unknown. The present study aimed to assess responses of type 1 diabetes patients to a dietary salt load with regard to BP, extracellular fluid volume (using precise iohexol measurements), and CD163+ macrophage and lymphatic capillary density in skin biopsies. Also, macrophage expression of HLA-DR (a proinflammatory marker) and CD206 (an anti-inflammatory marker) was assessed. Type 1 diabetes patients (n = 8) showed a salt-sensitive BP increase without extracellular fluid volume expansion. Whereas healthy controls (n = 12), who had no BP increase, showed increased skin CD163+ and HLA-DR+ macrophages and dilation of lymphatic skin vasculature after the dietary salt load, these changes were absent (and in case of HLA-DR more heterogenic) in type 1 diabetes patients. In conclusion, we show that salt sensitivity in type 1 diabetes patients cannot be explained by the classical concept of extracellular fluid volume expansion. Rather, we open up a potential role for macrophages and the lymphatic system. Future studies on hypertension and diabetes need to scrutinize these phenomena.

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A High Salt Diet Alters Pressure-Induced Mechanical Activity of the Rat Lymphatics with Enhancement of Myogenic Characteristics

Abstract: The present ex vivo study suggest that collecting lymphatics of rats enhance myogenic activity and lymphatic pump efficiency to compensate for increase in lymph flow and/or pressure after 2 weeks salt loading.

Cited by 11 publications

References 26 publications

Fluid Osmolarity Acutely and Differentially Modulates Lymphatic Vessels Intrinsic Contractions and Lymph Flow

Fluid Osmolarity Acutely and Differentially Modulates Lymphatic Vessels Intrinsic Contractions and Lymph Flow

The interstitium conducts extrarenal storage of sodium and represents a third compartment essential for extracellular volume and blood pressure homeostasis

Salt-sensitive blood pressure rise in type 1 diabetes patients is accompanied by disturbed skin macrophage influx and lymphatic dilation—a proof-of-concept study

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