Clemizole and La salts ameliorate angiotensin II-induced glomerular hyperpermeability in vivo.

Angiotensin II (Ang II) induces marked, dynamic increases in the permeability of the glomerular filtration barrier (GFB) in rats. After binding to its receptor, Ang II elicits Ca influx into cells, mediated by TRPC5 and TRPC6 (transient receptor potential canonical type 5 and 6). Clemizole and La salts have been shown to block TRPC channels in vitro, and we therefore tested their potential effect on Ang II-induced glomerular hyperpermeability.

Sustained, delayed, and small increments in glomerular permeability to macromolecules during systemic ET-1 infusion mediated via the ET receptor.

Emerging evidence indicates that endogenous production of endothelin (ET)-1, a 21-amino acid peptide vasoconstrictor, plays an important role in proteinuric kidney disease. Previous studies in rats have shown that chronic administration of ET-1 leads to increased glomerular albumin leakage. The underlying mechanisms are, however, currently not known.

Glomerular hyperpermeability after acute unilateral ureteral obstruction: effects of Tempol, NOS, RhoA, and Rac-1 inhibition.

It is well known that proteinuria following urinary tract obstruction is mainly of a tubular nature. However, it is unknown whether there are also changes in glomerular permeability. In this study, we compared glomerular sieving coefficients (θ) of polydisperse fluorescein isothiocyanate (FITC)-Ficoll 70/400 following a 120- or 180-min unilateral ureteral obstruction (UUO) in anesthetized Sprague-Dawley rats.

Nitric oxide synthase inhibition causes acute increases in glomerular permeability in vivo, dependent upon reactive oxygen species.

There is increasing evidence that the permeability of the glomerular filtration barrier (GFB) is partly regulated by a balance between the bioavailability of nitric oxide (NO) and that of reactive oxygen species (ROS). It has been postulated that normal or moderately elevated NO levels protect the GFB from permeability increases, whereas ROS, through reducing the bioavailability of NO, have the opposite effect. We tested the tentative antagonism between NO and ROS on glomerular permeability in anaesthetized Wistar rats, in which the left ureter was cannulated for urine collection while simultaneously blood access was achieved.

Acute reactive oxygen species (ROS)-dependent effects of IL-1β, TNF-α, and IL-6 on the glomerular filtration barrier (GFB) in vivo.

This study was performed to investigate the immediate actions of the proinflammatory cytokines IL-1β, TNF-α, and IL-6 on the permeability of the glomerular filtration barrier (GFB) in rats and to test whether these actions are dependent upon the release of reactive oxygen species (ROS). In anesthetized rats, blood access was achieved and the left ureter was cannulated for urine collection. Rats were continuously infused intravenously with either IL-1β (0.

mTOR inhibition with temsirolimus causes acute increases in glomerular permeability, but inhibits the dynamic permeability actions of puromycin aminonucleoside.

Inhibitors of the mammalian target of rapamycin (mTORi) can produce de novo proteinuria in kidney transplant patients. On the other hand, mTORi has been shown to suppress disease progression in several animal models of kidney disease. In the present study, we investigated whether glomerular permeability can be acutely altered by the mTORi temsirolimus and whether mTORi can affect acute puromycin aminonucleoside (PAN) or angiotensin II (ANG II)-induced glomerular hyperpermeability.

Dynamic, size-selective effects of protamine sulfate and hyaluronidase on the rat glomerular filtration barrier in vivo.

The proteinuric actions of protamine sulfate (PS) have classically been, at least partly, attributed to alterations of the negatively charged glomerular endothelial glycocalyx. To investigate whether the charge-selective properties of the glomerular filtration barrier (GFB) would be altered by PS, we assessed the glomerular sieving of conventional, uncharged, polydispersed Ficoll (n-Ficoll) compared with charge modified, conformationally intact, anionic (carboxymethylated) Ficoll (a-Ficoll) before and after systemic infusions of PS in rats. For comparison, we also investigated the impact of hyaluronidase (hyase), which partially degrades the glycocalyx, on GFB permeability.

Extracellular fetal hemoglobin induces increases in glomerular permeability: inhibition with α1-microglobulin and tempol.

Extracellular fetal hemoglobin (HbF) and adult hemoglobin (HbA) are proinflammatory and generate ROS. Increased plasma levels of extracellular HbF have recently been reported to occur in early preeclampsia. α1-Microglobulin (A1M) is a physiological heme-binding protein and radical scavenger that has been shown to counteract vascular permeability increases induced by HbA in the perfused placenta.

Scavengers of reactive oxygen species, paracalcitol, RhoA, and Rac-1 inhibitors and tacrolimus inhibit angiotensin II-induced actions on glomerular permeability.

Systemic infusions of ANG II rapidly induce large, dynamic increases in the permeability of the glomerular filtration barrier (GFB) in rats. After binding to its receptor(s), ANG II generates reactive oxygen species (ROS) and produces Ca²⁺ influx into cells, leading to activation of a plethora of signaling cascades, including, e.g.

Rapid, dynamic changes in glomerular permeability to macromolecules during systemic angiotensin II (ANG II) infusion in rats.

The actions of systemic angiotensin II (ANG II) infusions on glomerular permeability were investigated in vivo. In anesthetized Wistar rats (250-280 g), the left ureter was cannulated for urine collection, while simultaneously blood access was achieved. Rats were continuously infused intravenously with either of four doses of ANG II ranging from 16 ng·kg(-1)·min(-1) (Lo-ANG II) to 1.

Reduced diffusion of charge-modified, conformationally intact anionic Ficoll relative to neutral Ficoll across the rat glomerular filtration barrier in vivo.

The glomerular filtration barrier (GFB) is commonly conceived as a negatively charged sieve to proteins. Recent studies, however, indicate that glomerular charge effects are small for anionic, carboxymethylated (CM) dextran vs. neutral dextran.

Transient and sustained increases in glomerular permeability following ANP infusion in rats.

The present study was performed to investigate the effects of systemic atrial natriuretic peptide (ANP) infusion on the glomerular permeability to macromolecules in rats. In anesthetized Wistar rats (250-280 g), the left urether was cannulated for urine collection while simultaneously blood access was achieved. Rats were continuously infused intravenously with ANP [30 ng·kg(-1)·min(-1) (Lo-ANP; n=8) or 800 ng·kg(-1)·min(-1) (Hi-ANP; n=10)] or 0.

Acute hyperglycemia induces rapid, reversible increases in glomerular permeability in nondiabetic rats.

This study was performed to investigate the impact of acute hyperglycemia (HG) on the permeability of the normal glomerular filtration barrier in vivo. In anesthetized Wistar rats (250-280 g), the left ureter was catheterized for urine collection, while simultaneously blood access was achieved. Rats received an intravenous (iv) infusion of either 1) hypertonic glucose to maintain blood glucose at 20-25 mM (G; n = 8); 2) hypertonic glucose as in 1) and a RhoA-kinase inhibitor (Y-27632; Rho-G; n = 8); 3) 20% mannitol (MANN; n = 7) or 4) hypertonic (12%) NaCl to maintain plasma crystalloid osmotic pressure (pi(cry)) at approximately 320-325 mosmol/l (NaCl; n = 8) or 5) physiological saline (SHAM; n = 8).

Loss of size selectivity of the glomerular filtration barrier in rats following laparotomy and muscle trauma.

Posttraumatic microalbuminuria may be caused by either charge- or size-selective alterations in the glomerular filtration barrier, or both, and/or to a reduction in proximal tubular protein reabsorption. This study was performed to elucidate the pathophysiology of the increases in glomerular permeability occurring in rats exposed to a laparotomy or to a laparotomy and muscle trauma. In anesthetized Wistar rats (250-280 g), the left ureter was cannulated for urine collection, while simultaneously blood access was achieved.

Unaltered size selectivity of the glomerular filtration barrier in caveolin-1 knockout mice.

The transfer of albumin from blood to tissue has been found to be increased in caveolin-1 knockout (KO) mice. This has been considered to reflect increased microvascular permeability, conceivably caused by an increased endothelial production of nitric oxide (NO) in these mice. To investigate whether such an increase in NO production would also affect glomerular barrier characteristics, the glomerular sieving coefficients (theta) to neutral FITC-Ficoll 70/400 (molecular radius 13-90 A) were determined in caveolin-1 KO mice vs.

Effects of early endotoxemia and dextran-induced anaphylaxis on the size selectivity of the glomerular filtration barrier in rats.

This study was performed to investigate the glomerular permeability alterations responsible for the microalbuminuria occurring in endotoxemia and during anaphylactic shock. In anesthetized Wistar rats, the left ureter was catheterized for urine collection while, simultaneously, blood access was achieved. Endotoxemia was induced by lipopolysaccharide (LPS) from Escherichia coli, and glomerular permeability was assessed at 60 and 90 (n = 7) and 120 (n = 7) min.

Size and charge selectivity of the glomerular filter in early experimental diabetes in rats.

Microalbuminuria is an early sign of diabetic nephropathy. The aim of the present study was to investigate whether the changes of the glomerular filtration barrier in early experimental diabetes are due to size- or charge-selective alterations. Wistar rats, made diabetic by streptozotocin (STZ) and having their blood glucose maintained at approximately 20 mM for 3 or 9 wk, were compared with age-matched controls.

Arterial remodeling and plasma volume expansion in caveolin-1-deficient mice.

Caveolin-1 (Cav-1) is essential for the morphology of membrane caveolae and exerts a negative influence on a number of signaling systems, including nitric oxide (NO) production and activity of the MAP kinase cascade. In the vascular system, ablation of caveolin-1 may thus be expected to cause arterial dilatation and increased vessel wall mass (remodeling). This was tested in Cav-1 knockout (KO) mice by a detailed morphometric and functional analysis of mesenteric resistance arteries, shown to lack caveolae.

Screening history of women in Malmö with invasive cervical cancer.

Objectives: Cervical cancer is one of the most common forms of cancer among women. Cytological screening and follow-up are potentially effective procedures for preventing the development of - and mortality from - cervical cancer. The purpose of this study was to investigate the screening history of women diagnosed with cervical cancer with the aim of improving the screening programme.

Disproportionally low clearance of macromolecules from the plasma to the peritoneal cavity in a mouse model of peritoneal dialysis.

Background: This study was performed to establish a model for quantitative measurements of a number of basic peritoneal transport parameters, particularly transperitoneal clearances (Cl) of macromolecules, during mouse peritoneal dialysis.

Methods: Mice were anaesthetized using 3% isofluorane inhalation anaesthesia. The right jugular vein and the left femoral artery were cannulated for infusion and sampling purposes and for registration of (mean) arterial blood pressure.

Nature of glomerular capillary permeability changes following acute renal ischemia-reperfusion injury in rats.

This study was performed to evaluate the alterations of glomerular filtration barrier characteristics following acute renal ischemia-reperfusion (I/R). Ischemia was induced in anesthetized rats by unilateral renal artery occlusion for either 20 or 60 min, followed by reperfusion during 20 or 60 min, respectively, with the contralateral kidney serving as control. Sieving coefficients (theta) were obtained by analyzing Ficoll [mol.

Aquaporin-1 plays an essential role in water permeability and ultrafiltration during peritoneal dialysis.

The water channel aquaporin-1 (AQP1) is considered as the molecular counterpart of the ultrasmall pore predicted by the three-pore model of fluid transport across the peritoneal membrane. However, the definitive proof of the implication of AQP1 in solute-free water transport, sodium sieving, and ultrafiltration (UF) during peritoneal dialysis (PD) is lacking, and the effects of its deletion on the structure of the membrane are unknown. Using real-time reverse transcriptase-polymerase chain reaction and immunogold electron microscopy, we showed that AQP1 is the most abundant member of the AQP gene family expressed in the mouse peritoneum, and the only one located in the capillary endothelium.

Transvascular protein transport in mice lacking endothelial caveolae.

Caveolae are Omega-shaped vesicular structures postulated to play a role in transvascular protein transport. Studies on mice lacking endothelial caveolae, caveolin-1 knockout (Cav-1-KO) mice, indicate increased macromolecular transport rates. This was postulated to be due to the appearance of an alternative pathway.

Effects of glomerular filtration rate on Ficoll sieving coefficients (theta) in rats.

The purpose of the present study was to assess the role of diffusion and convection during filtration of Ficoll across the glomerular filter by comparing glomerular sieving coefficients (theta) to neutral fluorescein isothiocyanate (FITC)-Ficoll 70/400 obtained at low (hydropenic) vs raised (normal) glomerular filtration rates (GFRs). The theta for FITC-Ficoll was determined in anesthetized Wistar rats (304 +/- 18 g) following laparotomy and cannulation of the ureters, used for urine sampling. After surgery, GFR was 1.

Glomerular filtration rate dependence of sieving of albumin and some neutral proteins in rat kidneys.

The size and charge-selective properties of the glomerular barrier are partly controversial. Glomerular sieving coefficients (theta) for proteins have rarely been determined noninvasively before in vivo. Therefore, theta was assessed vs.