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The tubuloglomerular feedback (TGF) mechanism modulates renal hemodynamics and glomerular filtration rate in individual nephrons. Our study aimed to evaluate the TGF‐induced vascular responses by inhibiting Na‐K‐2Cl co‐transporters and sodium‐glucose co‐transporters in rats. We assessed cortical hemodynamics with high‐resolution laser speckle contrast imaging, which enabled the evaluation of blood flow in individual microvessels and analysis of their dynamical patterns in the time‐frequency domain. We demonstrated that a systemic administration of furosemide abolishes TGF‐mediated hemodynamic responses. Furthermore, we showed that the local microcirculatory blood flow decreased, and the TGF‐induced hemodynamic oscillations were sustained but weakened after inhibiting sodium‐glucose co‐transporters in Sprague–Dawley rats. [ABSTRACT FROM AUTHOR]

Abstract The tubuloglomerular feedback (TGF) mechanism modulates renal hemodynamics and glomerular filtration rate in individual nephrons. Our study aimed to evaluate the TGF‐induced vascular responses by inhibiting Na‐K‐2Cl co‐transporters and sodium‐glucose co‐transporters in rats. We assessed cortical hemodynamics with high‐resolution laser speckle contrast imaging, which enabled the evaluation of blood flow in individual microvessels and analysis of their dynamical patterns in the time‐frequency domain. We demonstrated that a systemic administration of furosemide abolishes TGF‐mediated hemodynamic responses. Furthermore, we showed that the local microcirculatory blood flow decreased, and the TGF‐induced hemodynamic oscillations were sustained but weakened after inhibiting sodium‐glucose co‐transporters in Sprague–Dawley rats.

Midkine is a low-molecular-weight heparin-binding protein that is strongly expressed mainly in the midgestation period and has various physiological activities such as in development and cell migration. Midkine has been reported to be strongly expressed in cancer cells and in inflammation and repair processes, and to be involved in the pathogenesis of various diseases. However, its role in the lung is poorly understood. In this study, we analyzed the clinical characteristics of idiopathic pulmonary fibrosis patients in relation to midkine expression and used a mouse bleomycin-induced pulmonary fibrosis model to investigate the role of midkine in pulmonary fibrosis. In the idiopathic pulmonary fibrosis patients, the serum midkine level was significantly higher than in healthy subjects, and midkine levels in the serum and bronchoalveolar lavage (BAL) fluid correlated positively with the percentage of inflammatory cells in the BAL fluid. In wild-type mice, intratracheal bleomycin administration increased midkine expression in lung tissue. Additionally, compared with wild-type mice, midkine-deficient mice showed low expression of both collagen and α-smooth muscle actin, as well as a low value for the pathological lung fibrosis score after bleomycin administration. Furthermore, the total cell count and lymphocyte percentage in the BAL fluid, as well as TNF-a and transforming growth factor-α expression in lung tissue, were significantly lower in the midkine-deficient mice compared with wild-type mice. These results suggest that midkine is involved in the development of pulmonary fibrosis by regulating inflammatory cell migration into the lung, and TNF-a and transforming growth factor-α expression. [ABSTRACT FROM AUTHOR]

Fetuses of pregnant ewes, which were subtotally nephrectomized prior to mating, were studied to assess whether mild maternal renal impairment would affect fetal tubuloglomerular feedback (TGF) under control conditions and after the inhibition of macula densa-derived nitric oxide (NO). Based on previous observations we hypothesized that, the TGF curve of fetuses of subtotally nephrectomized (STNx) ewes would resemble that of a volume expanded fetus with a high production rate of NO and that inhibition of neuronal nitric oxide synthase (nNOS) would increase the sensitivity of the TGF system in these fetuses. Renal function studies were performed on anaesthetized fetal sheep (133-140 days gestation; term ~150 days; Isoflurane 2-4% in oxygen). Fetuses were removed from the uterus and placed in a water bath (39.5°C) while maintaining umbilical blood flow. Glomerular filtration rate (GFR) and urine flow rate were markedly increased in fetuses of STNx ewes compared to fetuses of untreated ewes. Interestingly, and contrary to our hypothesis, the fetuses of STNx ewes exhibited no difference in TGF sensitivity in the presence or absence of 7-nitroindazole (7NI; nNOS inhibitor), compared to fetuses of untreated ewes, although sensitivity and reactivity increased in both groups after 7NI. There was however, a decrease in the stop flow pressure and net filtration pressure with an increase in the filtration coefficient (Kf). These factors suggest that maternal renal impairment drives the glomerular hypertrophy which has previously been found to be present in the neonatal period. Thus, we conclude that at ~138 days gestation, the fetal kidney has matured functionally and fetuses of STNx ewes are able to maintain fluid and electrolyte homeostasis even in the presence of increased transplacental flux., (© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)