[Renal vein thrombosis: Pathogenesis, pathophysiology, and therapy].
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Adrenal Cortex Hormones↗
Biomedical subjects
Toshikazu Takabatake
Publications and source records attributed to Toshikazu Takabatake.
Underrecognition of the severity of asthma and undertreatment of asthma in a rural area of Japan.
BACKGROUND AND AIM: Revised guidelines were released in Japan in 2003 for the assessment, treatment, and management of adult asthmatics, and similar guidelines for child asthmatics were released in 2002. We reassessed the severity and possible undertreatment of asthma according to these guidelines in stable asthmatics. METHODS: We reviewed medical records of 861 well-controlled asthmatic patients who, in April through June 2004 were cared for by 47 pulmonologists at 29 medical centers and 13 asthma clinics in a rural community in the San-in area of Japan. The physician obtained completed medical records about their symptoms and current treatment of the subjects, 726 adult and 135 children (aged 6 years or older) who were in stable condition and had had no exacerbations in the previous 3 months. The severity of asthma and current treatment for each patient were assessed according to the newly revised Japanese guidelines for the assessment, treatment, and management of adult and child asthmatics. RESULTS: In adult and child asthmatics, the percentage of predicted forced expiratory volume at 1 second (FEV1.0) was smaller and has a narrower distribution range than the percentage of predicted peak expiratory flow (PEF). When the severity of asthma was classified according to symptoms alone, 50% and 35% of those classified as mildly asthmatics patients with adults and children, respectively, had moderate to severe airflow limitation. Inhaled corticosteroids were prescribed to 90.6% of adult and 14.9% of child patients. When we compared the treatments that patients were actually receiving against the optimal treatments indexed according to a combined symptoms-FEV1.0 classification, we found that 49% of adult asthmatics were overtreated, 21% were properly treated, and 30% were undertreated. Among children, the respective percentages were 35%, 25%, and 40%. CONCLUSION: In well-controlled adult and child asthmatics, the severity of asthma is poorly judged when symptoms alone are considered. We suggest that the severity of asthma should be assessed through a combination of symptoms and the measurement of FEV1.0 during office visits. We also suggest that the proper dose of inhaled steroid needed to maintain stable conditions should be judged according to this combined symptoms-FEV1.0 classification.
Administration, Inhalation↗
Enhanced sympathetic control of renal function in rats congenic for the hypertension-related region on chromosome 1.
Recent studies suggest that a quantitative trait locus (QTL) for blood pressure (BP) on rat chromosome 1 is associated with exaggerated sympathetic nervous activity. The aim of the present study was to examine whether this QTL can affect BP by altering sympathetic control of renal function. Male stroke-prone spontaneously hypertensive rats of Izumo origin (SHRSP/Izm), Wistar-Kyoto rats (WKY/Izm) and rats from a WKY/Izm congenic strain that contains an SHRSP/Izm chromosomal segment between D1Wox29 and D1Arb21 (WKYpch1.0) were used. Clearance and micropuncture experiments were performed in anaesthetized rats after acute unilateral renal denervation (DN). Mean BP in sham-operated WKYpch1.0 was significantly higher than that in WKY/Izm. The DN procedure elicited a greater reduction in renal noradrenaline levels in SHRSP/Izm and WKYpch1.0 than in WKY/Izm. In both SHRSP/Izm and WKYpch1.0, DN decreased renal vascular resistance and filtration fraction, whereas it increased renal blood flow and urinary and fractional excretion of sodium. Unilateral renal denervation did not affect these parameters in WKY/Izm. Unilateral renal denervation decreased the tubuloglomerular feedback (TGF) responsiveness only in SHRSP/Izm, whereas it increased the non-perfused early proximal flow rate in SHRSP/Izm and WKYpch1.0. The results of the present study indicate that the renal sympathetic nervous system exerts enhanced tonic control of the renal vasculature and tubular function in SHRSP/Izm and WKYpch1.0, but not in WKY/Izm. Neural impact on the TGF response in WKYpch1.0 is indiscernible. Thus, a gene or genes in the QTL may influence BP, at least in part, through renal vasoconstriction and sodium retention mediated by the enhanced activity of the renal sympathetic nerves.
Animals↗
Effects of vasopeptidase inhibition on renal function and tubuloglomerular feedback in spontaneously hypertensive rats.
Vasopeptidase inhibitors are a novel class of antihypertensive agents that concomitantly inhibit angiotensin converting enzyme and neutral endopeptidase. Our purpose was to investigate the effects of omapatrilat, a vasopeptidase inhibitor, on renal function and tubuloglomerular feedback (TGF) response in anesthetized 9-10-week-old spontaneously hypertensive rats (SHR). Intravenous injection of omapatrilat at 10 micromol/kg decreased systemic blood pressure and renal vascular resistance. Renal plasma flow was unchanged, whereas glomerular filtration rate (GFR) and filtration fraction (FF) were reduced. Increased urinary sodium excretion of tubular origin was observed. These parameters remained unaltered with vehicle treatment. Micropuncture study revealed that the maximal reduction of early proximal flow rate (EPFR) induced by orthograde perfusion of Henle's loop with artificial tubular fluid (ATF) was significantly reduced by omapatrilat treatment (28.5+/-3.1% vs. 72.0+/-2.8% of control) and was not significantly changed in the vehicle-treated group (vehicle 70.8+/-1.7% vs. control 71.0+/-2.1%). EPFR at zero perfusion was comparable between omapatrilat and vehicle treatment (29.7+/-2.2 vs. 31.3+/-2.1 nl/min, respectively). Luminal perfusion of 10(-4) mol/l 7-nitroindazole in ATF abrogated the blunting of TGF response by omapatrilat but elicited no change in the vehicle-treated group. The suppression of the TGF mechanism and the reduction in FF suggest that omapatrilat respectively dilates the afferent and efferent arterioles. Under such conditions, reduction of GFR may indicate a fall in intraglomerular pressure. The restoration of nitric oxide signaling in the juxtaglomerular apparatus of SHR seems to participate in the inhibition of TGF by omapatrilat. These findings suggest that omapatrilat may provide a novel approach to the treatment of systemic and glomerular hypertension.
Animals↗
Effects of uroguanylin, an intestinal natriuretic peptide, on tubuloglomerular feedback.
Uroguanylin is an endogenous peptide that stimulates cyclic guanosine monophosphate (cGMP) production via the activation of guanylate cyclase C (GC-C) in the intestine and kidney. A high salt diet, but not intravenous salt load, enhances the secretion of biologically active uroguanylin from the intestine and increases its concentration in plasma and urine. Our purpose is to clarify the effect of uroguanylin on renal microcirculation and the tubuloglomerular feedback (TGF) mechanism. Clearance and micropuncture experiments were performed in anesthetized rats. TGF responsiveness was assessed in superficial nephrons by measuring the changes of early proximal flow rate (EPFR) in response to orthograde loop perfusion at 40 nl/min with artificial tubular fluid (ATF). Reductions in EPFR induced by loop perfusion during intravenous infusion of uroguanylin at the rate of 10 and 50 nmol/kg/h were similar yet significantly less than that during the control period (33+/-3% and 35+/-3% vs. 47+/-3%, p<0.05). Intraluminal application of uroguanylin at 10(-7) and 10(-5) mol/l in ATF decreased EPFR by 40+/-3% and 33+/-7%, respectively, with the latter value being significantly less than the control (p<0.05). Intravenous infusion of uroguanylin did not significantly change whole kidney function. Administration of atrial natriuretic peptide (ANP), which activates GC-A and B, significantly suppressed TGF-mediated EPFR reduction either intravenously (10 nmol/kg/h) or intraluminally (10(-5) mol/l in ATF) (9+/-3% and 13+/-2% vs. 47+/-3% of the control, p<0.05). In conclusion, uroguanylin clearly suppresses TGF both through intravenous and intraluminal routes, although the effects on glomerular microcirculation and whole kidney function are far less than those of ANP.
Animals↗
Effects of a nucleoside transporter inhibitor, dilazep, on renal microcirculation in rats.
Adenosine, one of the endogenous modulators in renal hemodynamics, has recently been shown to be a mediator of tubuloglomerular feedback (TGF). Dilazep augments endogenous adenosine actions by blocking its cellular uptake. Our purpose in the present study was to clarify the effects of dilazep on renal microcirculation and the TGF mechanism. Clearance and micropuncture experiments were performed in anesthetized rats. TGF responsiveness was assessed in superficial nephrons by measuring the changes of early proximal flow rate (EPFR) in response to loop perfusion at 0-40 nl/min with artificial tubular fluid (ATF). Under dilazep administration (0.3 mg/kg+0.3 mg/kg/h i.v.) systemic BP and GFR were decreased and renal plasma flow was unaltered; as a result, the filtration fraction tended to decrease (p=0.076). Renal vascular resistance was reduced, but not to a significant degree. The reduction in EPFR by loop perfusion was similar between controls (47 +/- 2%) and rats administered dilazep i.v. (44 +/- 5%). Intraluminal application of dilazep in ATF suppressed TGF-mediated EPFR reduction to by 46 +/- 4%, 43 +/- 7%, and 37 +/- 3% at dilazep concentrations of 10(-6), 10(-5), and 10(-4) mol/l, respectively. TGF suppression with 10(-4) mol/l dilazep was reversed by co-perfusion of 10(-5) mol/l DMPX, a selective adenosine A2 receptor antagonist. DMPX alone did not affect TGF response. In conclusion, these results indicate that systemic dilazep dilates postglomerular arterioles and does not affect TGF, and thus reduces GFR. A pharmacological concentration of dilazep applied to single nephrons clearly attenuates TGF, indicating afferent arteriolar vasodilatation. Extracellular adenosine augmented by dilazep dilates glomerular vessels at both afferent and efferent sites, probably via the activation of A2 receptors.
Animals↗
Systemic capillary leak syndrome.
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Capillary Leak Syndrome↗
Anti-apoptotic effect of atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, on cardiac myocytes through protein kinase C activation.
Pleiotropic effects of statins, which are independent of lipid lowering, have been reported. In the present study, we examined the effect of a statin on apoptosis of adult rat cultured cardiac myocytes. We used the protein kinase C (PKC) inhibitors staurosporine (1 micro mol/L), chelerythrine (10 micro mol/L) and rottlerin (5 micro mol/L) to induce myocyte apoptosis. The effect of atorvastatin (10(-7) g/mL), a statin, on myocyte apoptosis induced by these PKC inhibitors was examined. All these PKC inhibitors markedly increased the percentage of terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL)-positive myocytes. This increase was significantly suppressed by atorvastatin treatment. Both chelerythrine and rottlerin induced subcellular translocation of PKCdelta and elevated caspase-3 activity in myocytes. The changes in the subcellular distribution of PKCdelta and caspase-3 activity induced by these PKC inhibitors were suppressed by atorvastatin treatment. The results of the present study suggest that the inhibitory effect of atorvastatin on apoptosis of adult rat cardiac myocytes induced by the PKC inhibitors is through activation of PKCdelta pathway.
Animals↗