Mononuclear Phagocyte System Depletion Blocks Interstitial Tonicity-Responsive Enhancer Binding Protein/Vascular Endothelial Growth Factor C Expression and Induces Salt-Sensitive Hypertension in Rats

We showed recently that mononuclear phagocyte system (MPS) cells provide a buffering mechanism for salt-sensitive hypertension by driving interstitial lymphangiogenesis, modulating interstitial Na(+) clearance, and increasing endothelial NO synthase protein expression in response to very high dietary salt via a tonicity-responsive enhancer binding protein/vascular endothelial growth factor C regulatory mechanism. We now tested whether isotonic saline and deoxycorticosterone acetate (DOCA)-salt treatment leads to a similar regulatory response in Sprague-Dawley rats. Male rats were fed a low-salt diet and received tap water (low-salt diet LSD), 1.0% saline (high-salt diet HSD), or DOCA+1.0% saline (DOCA-HSD). To test the regulatory role of interstitial MPS cells, we further depleted MPS cells with clodronate liposomes. HSD and DOCA-HSD led to Na(+) accumulation in the skin, MPS-driven tonicity-responsive enhancer binding protein/vascular endothelial growth factor C-mediated hyperplasia of interstitial lymph capillaries, and increased endothelial NO synthase protein expression in skin interstitium. Clodronate liposome MPS cell depletion blocked MPS infiltration in the skin interstitium, resulting in unchanged tonicity-responsive enhance binding protein/vascular endothelial growth factor C levels and absent hyperplasia of the lymph capillary network. Moreover, no increased skin endothelial NO synthase protein expression occurred in either clodronate liposome-treated HSD or DOCA-salt rats. Thus, absence of the MPS-cell regulatory response converted a salt-resistant blood-pressure state to a salt-sensitive state in HSD rats. Furthermore, salt-sensitive hypertension in DOCA-salt rats was aggravated. We conclude that MPS cells act as onsite controllers of interstitial volume and blood pressure homeostasis, providing a local regulatory salt-sensitive tonicity-responsive enhancer binding protein/vascular endothelial growth factor C-mediated mechanism in the skin to maintain normal blood pressure in states of interstitial Na(+) and Cl(-) accumulation. Failure of this physiological extrarenal regulatory mechanism leads to a salt-sensitive blood pressure response

Verteilung von Umweltchemikalien in einem standardisierten oekologischen System Vergleich und Optimierung von Rechenmodellen anhand von Ergebnissen aus Experimenten

The fate of the following test chemicals in an aquatic ecosystem was investigated: 2 optical Brighteners, Trichlorbenzene, Nonylphenol, Dodecylphthalimide, Basic Green 4, Direct Blue 86, Acid Red 183 and a cationic surfactant. The following tasks were completed: - Development of analytical methods for determination of the compounds in various environmental compartments; - determination of the parameters for the important processes like hydrolysis, photolysis and biodegradation; - contamination of an artificial outdoor pond with the compounds and measuring the substance concentrations in the pond compartments with time; - comparison of experimental data with model calculations and optimization of the fugacity model used with respect to the results. (orig.)Das Umweltverhalten folgender Testchemikalien in einem aquatischen System wurde untersucht: optische Aufheller, Trichlorbenzol, Nonylphenol, Dodecylphtalimid, Acid Red 183, Direct Blue 86, Basic Green 4 und ein kationisches Tensid. Dazu gehoerte insbesondere: - Die Entwicklung der entsprechenden Spurenanalytik der Substanzen aus verschiedenen Umweltmedien; -die Bestimmung der Parameter wichtiger Prozesse wie Photolyse, Bioabbau, Hydrolyse; - das Einsetzen der Substanzen in einen kuenstlichen Freilandteich und die Bestimmung der zeitl. Konzentrationsverlaeufe in den einzelnen Kompartimenten; - Vergleich der gemessenen Daten mit Modellrechnungen und Optimierung des verwendeten Fugazitaetsmodells anhand der Ergebnisse. (orig.)SIGLEAvailable from TIB Hannover: RN 8908(92-048) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekUmweltbundesamt, Berlin (Germany)DEGerman

Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism

In salt-sensitive hypertension, the accumulation of Na+ in tissue has been presumed to be accompanied by a commensurate retention of water to maintain the isotonicity of body fluids. We show here that a high-salt diet (HSD) in rats leads to interstitial hypertonic Na+ accumulation in skin, resulting in increased density and hyperplasia of the lymphcapillary network. The mechanisms underlying these effects on lymphatics involve activation of tonicity-responsive enhancer binding protein (TonEBP) in mononuclear phagocyte system (MPS) cells infiltrating the interstitium of the skin. TonEBP binds the promoter of the gene encoding vascular endothelial growth factor-C (VEGF-C, encoded by Vegfc) and causes VEGF-C secretion by macrophages. MPS cell depletion or VEGF-C trapping by soluble VEGF receptor-3 blocks VEGF-C signaling, augments interstitial hypertonic volume retention, decreases endothelial nitric oxide synthase expression and elevates blood pressure in response to HSD. Our data show that TonEBP-VEGF-C signaling in MPS cells is a major determinant of extracellular volume and blood pressure homeostasis and identify VEGFC as an osmosensitive, hypertonicity-driven gene intimately involved in salt-induced hypertensio