Angiotensin II (Ang II) as a vasoactive hormone may be involved in progressive renal interstitial fibrosis. We investigated the influence of Ang II on cell proliferation and synthesis of extracellular matrix (collagen I, III and fibronectin) in human renal fibroblasts derived from normal (TK 173 cell line) and fibrotic (TK 188 cell line) kidneys which possess both Ang II type l and type 2 (AT1 and AT2) receptors. Incubation of the cells with Ang II increased the cell proliferation and the synthesis of extracellular matrix significantly in both cell lines. However, proliferation and extracellular matrix synthesis showed a greater increase in the cells derived from the fibrotic kidney. The Ang II mediated effect on cell proliferation and extracellular matrix synthesis was diminished in the presence of the AT1 receptor blocker losartan in both cell lines. No inhibition was observed using the AT2 receptor blocker PD123319. Ang II induced cell proliferation could be completely inhibited by incubation with human TGF-beta1 antibody. Incubation with Ang II did not affect TGF beta 1 production but in untreated cells TGF-beta 1 content was higher in the cells derived from the fibrotic kidney. This might be the reason for the more sensitive reaction on exposure to Ang II.

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In patients with congestive heart failure (CHF), a high prevalence of sleep-disordered breathing has been described. Cheyne-Stokes respiration (CSR) is present in up to 40% of patients with CHF. During the last decade, the medical treatment has been substantially improved. This study was designed to analyze the prognosis of CSR in modern-treated patients with CHF. For this purposes, in 57 patients with CHF who received modern treatment, a 5-year follow-up after initial full night polysomnography was performed. The mean follow-up period was 38 ± 18 months. Mean age was 62 ± 13 years and the mean ejection fraction was 25 ± 7 percent. Respiratory polygraphy revealed CSR with a respiratory disturbance index[5 per hour of sleep in 39 of 57 patients. Twelve patients died. CSR was only characterized by a tendency of worsening (log-rank test, p = 0.25). However, there was a significant difference toward positive outcome for patients who received cardiac resynchronization therapy (log-rank test, p = 0.036). Using Multivariate Cox's proportional hazard regression with the factors resynchronization and CSR, the effect of resynchronization was almost significant (p = 0.08). In conclusion, no significant change of Cheyne-Stokes prevalence can be found in our small group of modern-treated patients with CHF. Cardiac resynchronization therapy was associated with improved patient outcome.

Our results show a new sorbitol transport system in renal inner medullary interstitial cells, which is rather different from the described sorbitol permease in renal epithelial cells and from glucose transporters of the GLUT- and SGLT-family.

Sorbitol plays a major role in the maintenance of cell volume and functional integrity of several renal cells. Sorbitol synthesis takes place in inner collecting duct cells, whereas sorbitol dehydrogenase activity, which catalyzes the degradation of sorbiotol to fructose, could mainly be detected in renal inner medullary interstitial cells. Therefore, we supposed that interstitial cells would require a sorbitol transport into the cells. However, such a transport system has not yet been described. Therefore, we have characterized the uptake of sorbitol in immortalized interstitial TK-173 cells, which were derived from human renal fibroblasts. Comparable to fresh isolated renal fibroblasts of the rat, immortalized TK-173 cells have a high sorbitol dehydrogenase activity. In this report, a temperature-dependent sorbitol uptake with saturation kinetics could be detected in immortalized TK-173 cells. The transport is characterized by a high velocity (V_max 84 mmol/l × h) and an apparent K_m of 10 mmol/l. The sorbitol uptake is independent of membrane potential, sodium, and chloride. Altogether, the physiological characteristics of this sorbitol transport are different from those of the osmotically regulated sorbitol efflux from epithelial cells. These results provide evidence that TK-173 cells derived from renal fibroblasts have a specific sorbitol transport. Furthermore, these data suggest a cooperation between epithelial and interstitial cells concerning osmoregulation.