Effect of atrial natriuretic peptide and calcium antagonists on platelet-activating factor-induced contraction and intracellular calcium mobilization in rat mesangial cells.

We studied the effect of platelet-activating factor (PAF-acether) on rat mesangial cells (MC) and the intracellular mechanisms for PAF-acether-mediated MC activation. Contraction was measured as changes in planar cell surface area (PCSA), and intracellular free calcium concentration ([Ca2+]i) was measured as changes in the signal of the fluorescent indicator fura-2. PAF-acether induced a time- and dose-dependent reduction in PCSA and a dose-dependent increase in [Ca2+]i.

Platelet-activating factor mediates pancreatic function derangement in caerulein-induced pancreatitis in rats.

1. We have assessed the role of platelet-activating factor in caerulein-induced acute pancreatitis (four subcutaneous injections of caerulein at a dose of 20 micrograms/kg) by measuring platelet-activating factor levels in portal blood, pancreatic tissue and peritoneal exudate in rats with and without pancreatitis. 2.

Increased glomerular nitric oxide synthesis in gentamicin-induced renal failure.

Renal glomeruli isolated from normal rats and from rats with gentamicin-induced renal failure were incubated with substances that modify nitric oxide (NO) synthesis and the resulting changes in glomerular cyclic GMP (cGMP) levels were measured by radioimmunoassay. Glomeruli from normal and gentamicin-treated rats contained 0.17 +/- 0.

Renal catabolism of truncated glucagon-like peptide 1.

We have searched for the contribution of the kidney to the catabolism of glucagon-like peptide-1 (7-36)amide or tGLP-1 by analyzing the disappearance of the [125I]tGLP-1 both in vivo, from the plasma of bilaterally nephrectomized (BNX), ureteral-ligated (BUL) and normal rats and in vitro from the perfusate of an isolated rat kidney system. Also, we have measured the degradation of the peptide by the isolated renal tubules. Results from in vivo studies demonstrated that the disappearance half-time (t1/2) of [125I]tGLP-1 was significantly lower in the control than in BUL or BNX rats with the metabolic clearance rate (MCR) being higher in the control than in BUL and BNX group; no difference was found for both parameters between BUL and BNX rats.

Gentamicin nephrotoxicity in rats is not modified by verapamil.

To assess whether calcium could be involved in the gentamicin-induced nephrotoxicity, we have studied the effect of the calcium channel blocker verapamil on renal function in rats intoxicated by gentamicin. Male Wistar rats were divided in three groups. In group I (n = 7) they were injected with gentamicin 100 mg/kg body wt/day s.

A role for platelet-activating factor in endothelin-1-induced rat mesangial cell proliferation.

Endothelin-1 stimulated the release of bioassayable platelet-activating factor-like material and the incorporation of acetate to PAF in rat mesangial cells, in a dose-dependent manner, with an EC50 of about 10(-9) M. Endothelin-1 also stimulated dose dependently [3H]thymidine incorporation into DNA, protein synthesis and cell growth. The platelet-activating factor antagonists BN-52021 (10(-5) M), and alprazolam (10(-5) M), reduced significantly endothelin-1-stimulated thymidine incorporation into DNA, protein synthesis and cell growth.

Effects of the enantiomers of a new dihydropyridine derivative, S12968 and S12967, on renal functions in rats.

The aim of this study was to evaluate the effects of the two enantiomers of a new dihydropyridine, S12967 and S12968, on rat renal function. Male Wistar rats were injected intravenously with saline, S12967, or S12968 (0.1, 0.

Effect of gentamicin treatment on glutamine and lactate metabolism by the renal cortex of the rat.

The present study was performed to measure the uptake of main renal cortical fuel substrates (glutamine and lactate) and the release of the main renal cortical products (ammonia and glucose) by cortical slices from gentamicin-treated rats. Experiments were done in 2 groups of female Wistar rats (250 g): In gentamicin group (n = 13), rats were injected s.c.

Effect of extracellular volume expansion on erythrocyte cation transport in cirrhotic rats.

Erythrocyte intracellular Na+ and K+, and ouabain- and bumetanide-inhibitable Na+ efflux and 86Rb uptake have been measured in control and cirrhotic rats with or without extracellular volume expansion (EVE, saline, 3% body wt., 3 h). Non-expanded, cirrhotic rats showed a lower Na+ excretion (UNaV) than controls.

Effect of ouabain and hypothalamic, hypophysary inhibitory factor on rat mesangial cell proliferation.

The mitogenic effect of a low-molecular-weight, Na+,K(+)-ATPase inhibitory factor isolated from bovine hypothalamus and hypophysis (hypothalamic hypophysary inhibitory factor, HHIF) and ouabain on cultured rat mesangial cells was examined. Ouabain induced a potent stimulation of the [3H]thymidine incorporation to DNA, ranging from threefold for a dose of 10(-7) M to seven times for 10(-5) M. The amount of proteins per well also increased in a dose-dependent way, which was already significant from basal values for the lower dose used.

Effect of adenosine and adenosine analogues on cyclic AMP accumulation in cultured mesangial cells and isolated glomeruli of the rat.

1. Changes in intracellular levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) were studied in rat isolated glomeruli and cultured glomerular mesangial cells exposed to adenosine and to the preferential A1 receptor agonist N6-R-1-methyl-2-phenylethyl adenosine (R-PIA), or the potent A2 adenosine receptor agonist 5-(N-ethylcarboxamide)adenosine (NECA). 2.

Effects of reactive oxygen species on cultured rat mesangial cells and isolated rat glomeruli.

The effects of reactive oxygen species (ROS) on cultured rat mesangial cells were studied by measuring planar cell surface area (PCSA) after incubation with xanthine plus xanthine oxidase (XXO), in the presence of superoxide dismutase (SOD; 5 micrograms/ml) or catalase (CAT; 20 micrograms/ml), or after incubation with H2O2. Myosin light chain (MLC) phosphorylation was assessed in cells prelabeled with o-[32P]phosphoric acid and incubated with H2O2, after protein separation with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A possible intermediate role for platelet-activating factor (PAF) was analyzed by preincubation of the cells with a PAF antagonist BN 52021 (BN, 5 x 10(-5) M) and by measuring PAF-specific [3H]acetate incorporation and immunoassayable PAF.

Effect of adenosine A1 and A2 agonists and antagonists on cAMP and Ca2+ in cultured rat mesangial cells.

Rat glomeruli have been shown to exhibit A1 and A2 adenosine (ADO) receptors. Adenosine also contracts isolated glomeruli and cultured mesangial cells (MC). We studied the effect of the relatively selective ADO agonists R-N6-(1-methyl-1-phenylethyl)adenosine (R-PIA; A1) and 5'-(N-ethylcarboxamido)-adenosine (NECA; A2) on adenosine 3',5'-cyclic monophosphate (cAMP) levels and 45Ca influx in MC.

Adenosine stimulates Ca2+ fluxes and increases cytosolic free Ca2+ in cultured rat mesangial cells.

Adenosine has been associated with cellular Ca2+ metabolism in some cell types. Since adenosine is able to contract glomerular mesangial cells in culture, and since Ca2+ is the main messenger mediating contractile responses, we studied the effect of adenosine on 45Ca2+ movements into and out of mesangial cells and on the cytosolic free Ca2+ concentration ([Ca2+]i). Adenosine at 0.

Renal cortical intermediary metabolism in the recovery phase of postischemic acute renal failure in the dog.

Renal metabolism has been studied in eight dogs before and 48 hr after a 60-min period of renal ischemia induced by clamping the left renal artery with the simultaneous removal of the right kidney, and in 12 sham-operated animals. The study involved the measurement of renal uptake and production of lactate, glutamine, glutamate, alanine, ammonium, and oxygen, and the measurement of the tissue concentrations of ATP, glutamine, lactate, alpha-ketoglutarate, aspartate, and alanine in the renal cortex. Two days after a temporary renal ischemia, the remaining kidney showed a 22% decrease in glomerular filtration rate (GFR) and a 25% decrease in renal plasma flow.

Effect of platelet activating factor antagonist treatment on gentamicin nephrotoxicity.

To assess whether PAF could be involved in the gentamicin-induced nephrotoxicity, we have studied the effect of PAF antagonist BN-52021 on renal function in rats after gentamicin (GENTA) treatment. Experiments were completed in 21 Wistar rats divided into three groups: group GENTA was injected with gentamicin 100 mg kg(-1) body wt/day s.c.

Role of platelet-activating factor in hemodynamic derangements in an acute rodent pancreatic model.

Systemic hemodynamics were assessed in a model of experimental pancreatitis induced in rats by the retrograde injection of sodium deoxycholate, 40%, 1 mL/kg, in the pancreatic duct, using the radioactive microsphere technique before and 25 minutes after pancreatitis induction while blood pressure was stable (n = 10). A 55% decrease in cardiac out-put, a 14% decrease in heart rate, and a 3.3-fold increase in total peripheral resistances, without significant changes in blood pressure, were observed.

[The physiopathology of acute pancreatitis: the role of platelet-activating factor (PAF)].

PAF-acether (platelet-activating factor) is a vasoactive substance appearing in plasma under certain pathological circumstances. The aim of our study was to determine plasma, peritoneal exudate and tissular levels of PAF-acether in bile reflux acute necro-hemorrhagic pancreatitis (ANP) in the conscious rat 60 minutes after induction. As we have previously demonstrated, ANP causes overwhelming shock in conscious rats.

Is renal protection with calcium antagonists possible?

Organ protection is the main goal in the treatment of high blood pressure. Consequently, this protective capacity should be one of the main characteristics of any drug used in the treatment of hypertension. A renal protective agent should protect the kidney from intrinsic renal vasoconstrictors and exogenous agents, and should also protect, or at least delay, the decline in renal function in the presence of renal insufficiency, by mechanisms other than increasing glomerular filtration pressure.

A role for endothelin in the maintenance of post-ischaemic renal failure in the rat.

1. Endothelin (ET) has been shown to reduce glomerular filtration rate (GFR) and renal blood flow (RBF) and may therefore be a possible mediator of the reduction of GFR and RBF observed in post-ischaemic acute renal failure. 2.

[Hemodynamic changes in an acute pancreatitis experimental model in awaken rats].

The aim of the present study was to determine the hemodynamic effect of acute hemorrhagic pancreatitis in conscious rats. For this purpose, radioactive microspheres were used in 3 groups: control (n = 5); 25 min pancreatitis (n = 10); 50 min pancreatitis (n = 10), performing a basal and final (25 or 50 minutes postpancreatitis) hemodynamic study. Acute hemorrhagic pancreatitis was induced in 25 min and 50 min pancreatitis groups overwhelming shock with decrease of 55% in cardiac output, 58% in renal blood flow while total peripheral resistance increased in 342%.

Renal effects and mesangial cell contraction induced by endothelin are mediated by PAF.

The recently discovered vasoactive peptide endothelin and platelet activating factor (PAF) share similar renal effects. The purpose of the present series of experiments has been to analyze the functional relations between the effect of endothelin on renal function and glomerular and mesangial cell contraction and the production and actions of PAF in kidney. Endothelin 1 nmol/kg body wt induced a transient decrease of glomerular filtration rate (from 1.

Atrial natriuretic peptide in patients with acute myocardial infarction without functional heart failure.

The purpose of the present study was to measure plasma levels of atrial natriuretic peptide (ANP) in patients with acute myocardial infarction without heart failure, and also to assess the temporal sequence of changes of plasma ANP during the first hours of recovery from myocardial infarction. The study was performed in 22 patients who were admitted to the Intensive Care Unit with the diagnosis of acute myocardial ischaemia that had an evolution of less than 6 h. Blood samples were drawn on admission and at 1, 8, and 24 h, and plasma concentrations of ANP, renin, aldosterone, epinephrine, norepinephrine and vasopressin were measured.

Glomerular binding and contractile response to angiotensin II in rats with chronic experimental cirrhosis of the liver.

1. The effects of angiotensin II on glomerular filtration rate and renal plasma flow were studied in surgically instrumented conscious control and cirrhotic rats. In addition, angiotensin II binding and the contractile response to angiotensin II were studied in glomeruli isolated from cirrhotic and control rats.

Renal function derangements induced by portacaval anastomosis in normal rats.

The purpose of this study was to determine the renal function derangements that portacaval shunting caused in previously normal rats. Eight rats suffered a surgical portacaval shunt (PCS) and another 8 a sham operation (SHAM). Renal function was investigated by determining urinary volume, sodium, potassium, creatinine and aldosterone excretion, in basal conditions and after sodium overload.