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Biomedical subjects

E Kusano

Publications and source records attributed to E Kusano.

At least 37 records · Page 2Linked to original sources
PubMed2001

Nephron distribution of total low Km cyclic AMP phosphodiesterase in mouse, rat and rabbit kidney.

The activity of cAMP degradation enzyme, cAMP phosphodiesterase (cAMP PDE), in renal tubules is a critically important factor in determining cellular cAMP levels, particularly in response to hormones. In this study we examine the nephron distribution of cAMP PDE activity in the mouse, rat and rabbit kidney and important cellular regulators of cAMP PDE, namely calmodulin and adenosine triphosphate (ATP). We assayed total low Km cAMP PDE in microdissected tubule segments, using 10(-6) M (3H) cAMP as a substrate. Activities were expressed in fentomol cAMP hydrolyzed per minute per mm tubular length or per one glomerulus. The content of ATP was measured in outer medullary collecting duct and medullary thick ascending limb of Henle's loop with microbioluminescence assay using firefly luciferase. In mouse kidney, cAMP PDE was significantly higher in all tubular segments compared to glomerulus. Proximal convoluted tubule, proximal straight tubule, medullary thick ascending limb of Henle's loop (mTAL), and outer medullary collecting duct (OMCD) had intermediated activity. Greater cAMP PDE activity was detected in cortical ascending limb of Henle's loop (cTAL), cortical collecting duct and in distal convoluted tubule (DCT). The highest activity was found in connecting tubules. In rat, nephron distribution of cAMP PDE activities was similar to mouse, except that activity in glomeruli was higher than in mouse glomeruli. In rabbit, nephron distribution of cAMP PDE activities was different from those of mouse and rat. There was no single prominent segment with high cAMP PDE activity. DCT and cTAL showed low enzyme activity. Overall, the highest cAMP PDE activities were measured in the mouse and the lowest were measured in the rabbit nephrons, with those of rat nephron showing an intermediate activity. The maximum effective dose of the calmodulin antagonist, trifluoperazine (200 microM), inhibited cAMP PDE in all nephron segments from the rat kidney. However, there is no statistical significance of its inhibition among nephron segments. In OMCD and mTAL of the rat kidney, cAMP PDE activity was inhibited by ATP (5 mM to approximately 10 mM) which is far beyond the physiological concentartion of ATP in normal epithelial cell. Actual determinations of ATP in mTAL and OMCD were 0.1 mM and 0.17 mM, respectively. These observations show that distal segments of tubules have more active catabolism of cAMP than proximal segments. cAMP PDE in each nephron segment appear to be almost equally dependent on trifluoperazine-sensitive pathway that may reflect the Ca2+-calmodulin system. Cellular concentration of ATP might not be involved in the regulation of the total low Km cAMP PDE activity in rat mTAL and OMCD.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

[Prospective evaluation of renal function by serum cystatin-C: comparison with three other parameters of glomerular filtration rate].

Cystatin-C is a low-molecular-weight basic protein produced at a stable rate by all nucleated cells. It is freely filtered through the renal glomeruli and primarily catabolized in the proximal tubule cells. Since the serum cystatin-C concentration is not affected by muscle mass nor inflammation, it has been postulated to be an improved marker of glomerular filtration rate (GFR) compared with the serum creatinine level. To evaluate the clinical usefulness in terms of estimation of the glomerular filtration rate(GFR), we compared the serum cystatin-C concentration with other markers of GFR, such as serum levels of creatinine(SCr), alpha 1-microglobulin(alpha 1MG), and beta 2-microglobulin(beta 2MG). Their variations were analyzed based on 2-hour creatinine clearance (2hCCr) as a standard marker of GFR. The logarithmic value of serum cystatin-C level showed a stronger negative correlation(-0.959) with the logarithmic value of 2hCCr than that of other markers(-0.924, -0.942, -0.888; SCr, alpha 1MG, beta 2MG, respectively). Although beta 2MG showed the next strongest correlation with 2hCCr, it had a significantly lower sensitivity when detecting mild reduction of GFR. In addition, serum cystatin-C showed the greatest area under the curve of receiver-operating characteristic(ROC) of all GFR markers at both higher(90 ml/min.) and lower(70 ml/min.) cut-off value of 2hCCr. These data suggest that serum cystatin-C is useful for estimating GFR, even if the reduction of GFR is very mild.

Adult↗
PubMed2000

Erythropoietin regulates vascular smooth muscle cell apoptosis by a phosphatidylinositol 3 kinase-dependent pathway.

BACKGROUND: Recent studies have shown that several cytokines could induce apoptosis in vascular smooth muscle cells (VSMCs) via the induction of nitric oxide (NO). In the present study, we explored whether human recombinant erythropoietin (rHuEPO) has a modulatory effect of apoptosis on interleukin-1beta (IL-1beta) or NO donor sodium nitroprusside (SNP)-induced apoptosis in rat cultured VSMCs. METHODS: The quantitation of apoptosis among VSMCs was assessed by nuclear morphological analysis with fluorescent DNA-binding dye Hoechst 33258. Apoptotic changes were also confirmed by the detection of DNA fragmentation. The expression of EPO receptor (EpoR), cellular protein tyrosine phosphorylation, including EpoR and Janus kinase (JAK) 2, and the association of p85 subunit of phosphatidylinositol 3 kinase (PI3-kinase) to tyrosine-phosphorylated proteins, including EpoR, were explored by using Western blotting analysis combined in part with immunoprecipitation. RESULTS: rHuEPO inhibited the apoptosis induced by IL-1beta or SNP in a dose- and time-dependent manner. The anti-apoptotic effects of rHuEPO were diminished in the presence of a tyrosine kinase (TK) inhibitor genistein or anti-EpoR antibody. After stimulation with rHuEPO, EpoR and JAK 2 were tyrosine phosphorylated, and p85 subunits were associated with EpoR. Also, rHuEPO induced phosphorylation of Akt through a PI3-kinase-dependent pathway. The phosphorylation of Akt and the anti-apoptotic effects of rHuEPO were diminished in the presence of a PI3-kinase inhibitor, wortmannin. CONCLUSION: Our present study demonstrates that rHuEPO inhibites IL-1beta or SNP-induced VSMC apoptosis. The TK-dependent pathway, particularly the PI3-kinase-dependent pathway, seems to be critical to the countervailing effect of rHuEPO on IL-1beta and SNP-induced VSMC apoptosis.

Anemia↗
PubMed2000

Skin hemodynamics during change from supine to lateral position.

The purpose of this study was to identify the skin hemodynamics during the position change from supine to lateral in patients with neurodegenerative diseases. The participants were 19 patients with neurodegenerative diseases and 12 healthy volunteers. The alteration in the total concentration of oxyhemoglobin and deoxyhemoglobin, indicative of change in blood volume, was measured in the skin of the left flank by using a portable noninvasive tissue oxygen monitor by near-infrared spectroscopy. The positions were changed from the left and right lateral with a return to the supine between each procedure. In healthy volunteers, total hemoglobin concentration (skin blood volume) increased when the position changed from supine to left lateral and decreased when changed from supine to right lateral. The decreased skin blood volume gradually recovered after a change from the supine to the right lateral position in healthy volunteers. However, it did not recover in three sporadic olivopontocerebellar atrophy (OPCA) patients with marked autonomic dysfunction and one Parkinsonian patient with severe orthostatic hypotension. Our study identified that the intracutaneous blood was changing dynamically during the position change from supine to lateral and was regulated by autonomic nerve function.

Autonomic Pathways↗
PubMed2000

[High PTHrP level induced hypercalcemia and acute renal failure in a multiple myeloma patient].

Multiple myeloma causes various renal injuries by direct invasion of myeloma cells, AL amyloidosis and hypercalcemia. Hypercalcemia induced by myeloma has been thought to be a result of local osteolysis. Recently, however, it was noted that no significant difference existed in the degree of bone-destruction between hypercalcemic and normocalcemic multiple myeloma. The exact mechanisms of hypercalcemia induced by multiple myeloma remain unconfirmed. In the present study, we report a 70-year-old man, suffering from acute renal failure due to multiple myeloma and severe hypercalcemia. While the serum PTH level was low, PTHrP was markedly increased. Bone scintigraphy implied systemic increase in bone turnover in addition to cold spots corresponding to punched out lesions on bone Xp. After the intravenous administration of bisphosphonate, hypercalcemia and hot accumulation on bone scintigraphy were improved while the PTHrp level and bone destruction by myeloma cells were not improved. The present case suggests involvement of PTHrP in hypercalcemia of multiple myeloma.

Acute Kidney Injury↗
PubMed2000

[Comparison of plasma exchange (PEX) vs. double filtration plasmapheresis (DFPP) with or without steroid administration in a case of MPO-ANCA-positive immune complex type crescentic glomerulonephritis].

The effect of plasmapheresis(PP) monotherapy and PP with corticosteroid administration were evaluated in a male with crescentic glomerulonephritis(CrGN). On the first admission, since he was positive for both anti-neutrophil cytoplasmic myeloperoxydase autoantibody(MPO-ANCA) and circulating immune complex(IC), the treatment was started with PP alone to reduce these autoantibodies immediately. During two months, three series of PP were performed: three sessions of plasma exchange (PEX) with fresh frozen plasma(FFP), two sessions of double filtration plasmapheresis(DFPP), and then, another two sessions of PEX, respectively. ANCA remained suppressed for 4 weeks after the first series of PEX, and increased thereafter. Subsequent DFPP caused a rebound of ANCA titer while the second PEX suppressed ANCA, at least, for 1 week. Though creatinine clearance(Ccr) improved after the first PEX and this level was maintained, ANCA increased again after the second PEX. Therefore the patient was treated with methyl-prednisolone(m-PSL) semipulse therapy followed by mild cocktail therapy including prednisolone(PSL) at 20 mg/day and mizoribine at 100 mg/day. In two weeks, ANCA and IC became negative and Ccr improved further. When PSL was tapered off, the ANCA became positive again. Since ANCA was not suppressed and Ccr declined gradually even after re-administration of oral PSL at 30-40 mg/day, PP was superimposed on steroid therapy with 3 sessions of DFPP and PEX, respectively. Ccr was improved, but ANCA was not sufficiently decreased by DFPP. Subsequent PEX was more efficient than DFPP in reducing the ANCA level. However, m-PSL semipulse was eventually required for complete suppression of ANCA. Thus PP was partially effective, but not sufficient as monotherapy. However it was considered advantageous as an adjunct therapy to reduce the dose of immunosuppressive drugs in CrGN. As to the mode of PP, PEX with FFP appeared to be more effective than DFPP in reducing the plasma ANCA level.

Aged↗
PubMed1999

Human recombinant erythropoietin inhibits interleukin-1beta-stimulated nitric oxide and cyclic guanosine monophosphate production in cultured rat vascular smooth-muscle cells.

BACKGROUND: Recently rat vascular smooth-muscle cells (VSMC) have been shown to possess Epo receptor, and respond to various cytokines for producing nitric oxide (NO). In the present study we examined the effect of pharmacological dose of human recombinant erythropoietin (rHuEpo) on the IL-1beta-induced NO and cGMP production as well as inducible nitric oxide synthase (iNOS) in cultured rat VSMC. METHODS: Nitrite, a stable metabolite of NO, and intracellular cGMP contents were assayed by Griess method and enzyme immunoassay. iNOS mRNA expression was analysed by Northern blotting. RESULTS: RHuEpo inhibited IL-1beta-induced nitrite production in a dose- and time-dependent manner with concomitant changes of intracellular cGMP contents. On the other hand, rHuEpo did not inhibit atrial natriuretic peptide- (ANP) or sodium nitroprusside (SNP)-induced nitrite and cGMP production at all. While rHuEpo inhibited IL-1beta-induced iNOS mRNA expression, rHuEpo vehicle did not affect IL-1beta-induced iNOS mRNA expression. CONCLUSIONS: It is suggested that a pharmacological dose of rHuEpo inhibits IL-1beta-induced NO and cGMP production as well as iNOS mRNA expression, presumably via the Epo receptor.

Animals↗
PubMed1999

The effect of erythropoietin on interleukin-1beta mediated increase in nitric oxide synthesis in vascular smooth muscle cells.

OBJECTIVE: Recently, we observed that recombinant human erythropoietin (rHuEPO) inhibits the interleukin (IL)-1beta induced nitric oxide (NO) production and inducible NO synthase (iNOS) expression in cultured rat vascular smooth muscle cells (VSMC). The mechanisms of these inhibitory effects of rHuEPO were evaluated. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was performed to identify a specific erythropoietin receptor (EpoR). Tyrosine phosphorylation of phospholipase C (PLC) was analyzed by combination of immunoprecipitation and Western blotting. Protein kinase C (PKC) activities were analyzed by phosphorylation assay of myelin basic protein (MBP4-14). VSMC were incubated with test agents for 24 h and nitrite as a stable NO metabolite was measured. iNOS mRNA and protein expression was analyzed by Northern and Western blotting, respectively. RESULTS: RT-PCR analysis revealed that EpoR m-RNA was expressed; furthermore, it might be alternatively spliced in VSMC. rHuEPO induced tyrosine phosphorylation of PLC-gamma1 and activation of PKC. rHuEPO inhibited not only IL-1beta induced nitrite production, but also the expression of iNOS mRNA and protein. These inhibitory effects of rHuEPO were reversed in the presence of PKC inhibitors, calphostin C (1 pmol/l) or staurosporine (10 nmol/l). PKC activation by phorbol myristate acetate inhibited nitrite production. The inhibitory effect of rHuEPO on IL-1beta induced nitrite production was also eliminated in PKC depleted cells or in the existence of anti-EpoR antibody. CONCLUSION: rHuEPO inhibits IL-1beta induced NO production by suppressing iNOS mRNA and protein expressions through EpoR, and the PLC-gamma1 and PKC pathway may be involved.

Animals↗
PubMed1999

Incubation of OKP cells in low-K+ media increases NHE3 activity after early decrease in intracellular pH.

Chronic hypokalemia increases the activity of proximal tubule apical membrane Na+/H+ antiporter NHE3. The present study examined the effect of the incubation of OKP cells (an opossum kidney, clone P cell line) in control medium (K+ concn ([K+]) = 5.4 mM) or low-K+ medium ([K+] = 2.7 mM) on NHE3. The activity of an ethylisopropyl amiloride-resistant Na+/H+ antiporter, whose characteristics were consistent with those of NHE3, was increased in low-K+ cells beginning at 8 h. NHE3 mRNA and NHE3 protein abundance were increased 2.2-fold and 62%, respectively, at 24 h but not at 8 h. After incubation in low-K+ medium, intracellular pH (pHi) decreased by 0.27 pH units (maximum at 27 min) and then recovered to the control level. Intracellular acidosis induced by 5 mM sodium propionate increased Na+/H+ antiporter activity at 8 and 24 h. Herbimycin A, a tyrosine kinase inhibitor, blocked low-K+- and sodium propionate-induced activation of the Na+/H+ antiporter at 8 and 24 h. Our results demonstrate that low-K+ medium causes an early decrease in pHi, which leads to an increase in NHE3 activity via a tyrosine kinase pathway.

Acids↗
PubMed1999

AVP inhibits LPS- and IL-1beta-stimulated NO and cGMP via V1 receptor in cultured rat mesangial cells.

The present study examined how arginine vasopressin (AVP) affects nitric oxide (NO) metabolism in cultured rat glomerular mesangial cells (GMC). GMC were incubated with test agents and nitrite, and intracellular cGMP content, inducible nitric oxide synthase (iNOS) mRNA, and iNOS protein were analyzed by the Griess method, enzyme immunoassay, and Northern and Western blotting, respectively. AVP inhibited lipopolysaccharide (LPS)- and interleukin-1beta (IL-1beta)-induced nitrite production in a dose- and time-dependent manner, with concomitant changes in cGMP content, iNOS mRNA, and iNOS protein. This inhibition by AVP was reversed by V1- but not by oxytocin-receptor antagonist. Inhibition by AVP was also reproduced on LPS and interferon-gamma (IFN-gamma). Protein kinase C (PKC) inhibitors reversed AVP inhibition, whereas PKC activator inhibited nitrite production. Although dexamethasone and pyrrolidinedithiocarbamate (PDTC), inhibitors of nuclear factor-kappaB, inhibited nitrite production, further inhibition by AVP was not observed. AVP did not show further inhibition of nitrite production with actinomycin D, an inhibitor of transcription, or cycloheximide, an inhibitor of protein synthesis. In conclusion, AVP inhibits LPS- and IL-1beta-induced NO production through a V1 receptor. The inhibitory action of AVP involves both the activation of PKC and the transcription of iNOS mRNA in cultured rat GMC.

Animals↗
PubMed1999

[Factors related to the QT prolongation in chronic renal failure].

QT prolongation, a risk factor for arrhythmia and cardiac death, is observed in uremic patients. Though hypocalcemia, autonomic nerve dysfunction and cardiac hypertrophy are assumed to cause the uremic QT prolongation, the exact mechanism remains unspecified. We therefore examined factors related to the QT interval in chronic renal failure (CRF). Corrected QT interval (QTc) was significantly prolonged in CRF just before the induction of dialysis therapy (group A) compared with nephrotic syndrome with the intact or mildly impaired renal function (group B). QTc was also prolonged in acute renal failure (group C). Cardio-thoracic ratio, serum albumin and Ca correlated with QTc in group A, but not in B or C. A single HD session in group A failed to shorten QTc, despite a significant increase in serum Ca++. Autonomic dysfunction did not appear to be a major determinant of QT prolongation, since QTc was not different between diabetics and non-diabetics in group A and in chronic HD patients (group D). In group D, QTc did not correlate with SV1 + RV5 on ECG or left ventricular wall thickness (LVWT) on echocardiography. In another group of chronic HD patients (group E), there was no significant correlation between QTc and the parameters of left ventricular mass, plasma brain natriuretic peptide (BNP). However, in the patients subjected to repeated echocardiography in group D, QTc and LVWT changed in parallel. In a retrospective analysis of QTc in group D, QTc was maximally prolonged at the time of starting HD therapy, and gradually improved in the following 1-5 years in both diabetics and non-diabetics. In contrast, chronic CAPD patients (group F) revealed no improvement of QTc. Thus, uremic QT prolongation cannot be explained simply by any of the previously assumed factors, but appears to be affected by multiple factors, which are partially correctable by chronic HD therapy.

Autonomic Nervous System Diseases↗
PubMed1999

[A case of malignant hypertension in whom steroid improved renal function].

We report a case whose renal failure was due to malignant hypertension and in whom steroid facilitated the recovery of renal function. The patient, a 41-year-old man, was admitted to our hospital because of malaise and macrohematuria. On admission, his blood pressure was 270/160 mmHg. The plasma renin activity (PRA) and aldosterone were markedly elevated. Chest X-ray, echo cardiography and electrocardiogram revealed marked hypertrophy. Hypertensive retinopathy and arteriosclerotic change were noted on ophthalmoscopy. Because of renal dysfunction (blood urea nitrogen 45.6 mg/dl, serum creatinine 4.9 mg/dl with massive proteinuria and increased FENa, renal biopsy was performed on the 8th clinical day. The specimens showed slight proliferation of mesangial cells with mesangiolysis and interstitial cell infiltration, in addition to marked arteriosclerosis and partial collapse of the glomerular tuft. After the administration of a Ca antagonist and angiotensin converting enzyme inhibitor (ACE-I), his mean blood pressure decreased to 100-130 mmHg, and urinary protein decreased as well. Nevertheless, renal dysfunction remained unchanged during the following 3 weeks. Thus, prednisolone (PSL, 30 mg/day) was administered on the 22nd clinical day and renal function improved thereafter without a significant change in blood pressure. The improved renal function was maintained after PSL tapered off on the 184th clinical day. It is suggested that PSL might be the therapy of choice in malignant hypertension, when the renal function has not been improved by anti-hypertensive treatment alone.

Adult↗
PubMed1998

Atrial natriuretic peptide enhances IL-1 beta-stimulated nitric oxide production in cultured rat vascular smooth muscle cells.

OBJECTIVE: To elucidate the effect of atrial natriuretic peptide (ANP) on cytokine-induced nitric oxide (NO) production, we examined whether ANP affects IL-1 beta-stimulated NO production and inducible NO synthase (iNOS) mRNA expression in cultured rat vascular smooth muscle cells (VSMC). METHODS: VSMC were incubated with test agents for 24 h. The nitrite concentration of the culture medium, a stable-end product of NO, was measured by the column reduction method. NOS mRNA expression was analyzed by Northern blotting. The intracellular cAMP content was measured by enzyme immunoassay. cAMP-dependent kinase (PKA) activity was determined by a PKA assay system. RESULTS: IL-1 beta stimulated nitrite production in VSMC. ANP (10 nM to 1 mM) enhanced the nitrite production and iNOS mRNA expression in the presence of IL-1 beta. Both 8-bromo-guanosine 3',5'-cyclic monophosphate (8-br-cGMP) and dibutylyl adenosine 3',5'-cyclic monophate enhanced IL-1 beta-induced nitrite production. The effects of these two nucleotide donors on the nitrite production were not additive, suggesting a common pathway. KT 5720, an inhibitor of PKA, abolished the enhancement of nitrite production by ANP and 8-br-cGMP, while KT 5823, an inhibitor of cGMP-dependent protein kinase, did not inhibit the enhancement. In the in vitro assay 8-br-cGMP increased PKA activity. CONCLUSIONS: ANP and cGMP enhanced IL-1 beta-induced NO production in VSMC. PKA rather than PKG may be involved in the enhancement.

Animals↗
PubMed1997

A low-Na+ diet enhances expression of mRNA for epithelial Na+ channel in rat renal inner medulla.

The purpose of the present study was to determine whether the renal inner medulla expresses mRNA for the rat epithelial Na+ channel (rENaC) and, if so, to define its regulatory properties using a low-Na+ diet model. We detected alpha, beta and gamma subunit mRNA in rat renal inner medulla using reverse transcriptase-polymerase chain reaction (RT-PCR) with primers specific for rENaC alpha, beta and gamma subunits. Moreover, we have developed a specific probe for the alpha subunit using RT-PCR with rENaC alpha-subunit-specific primers. The resulting cDNA was verified by sequencing and was then used in Northern blot analysis of distal colon, whole kidney and inner medulla. The probe for the rENaC alpha subunit hybridized not only to distal colon RNA but also to inner medulla RNA derived from rats fed a normal diet. Furthermore, we examined the effect of a low-Na+ diet on alpha, beta and gamma subunit mRNA expression of rENaC using full-length cDNA as a probe. A marked elevation of rENaC alpha subunit mRNA abundance in the inner medulla was observed in response to a high plasma aldosterone concentration induced by dietary Na+ deprivation. On the other hand, neither beta nor gamma subunit mRNA expression was enhanced by a low-Na+ diet. From these results, it is suggested that rENaC is responsible for Na+ transport in the renal inner medulla and that is probably regulated via transcriptional control of the alpha subunit of ENaC.

Animals↗
PubMed1997

Arginine vasopressin inhibits interleukin-1 beta-stimulated nitric oxide and cyclic guanosine monophosphate production via the V1 receptor in cultured rat vascular smooth muscle cells.

BACKGROUND: It has been reported that various vasoactive substance modulate cytokine stimulated nitric oxide (NO) production in many cell types. OBJECTIVE: To examine the effects of arginine vasopressin (AVP) on the production of NO and cyclic GMP (cGMP), and on inducible nitric oxide synthase (INOS) in cultured rat vascular smooth muscle cells (VSMC). DESIGN: Because VSMC possess the V1 receptor which clauses vascular contraction and respond to various cytokines for producing NO, we used rat VSMC and selected interleukin-1 beta (IL-1 beta) as a potent stimulator of NO production among various cytokines. We also measured cGMP production, which is the final mediator of NO-induced vascular relaxation, in order to evaluate the physiologic meaning of the present study. METHODS: VSMC were incubated with test agents for 24 h except for a time-course study. Nitrite as a stable end product of NO was measured in the medium. Intracellular cGMP contents were assayed by enzyme immunoassay. INOS messenger RNA expression was analyzed by Northern blotting. RESULTS: AVP inhibited IL-1 beta-induced nitrite production in a dose- and time-dependent manner with concomitant changes in intracellular cGMP contents. On the other hand, AVP did not affect nitrite and cGMP production in the absence of IL-1 beta. Inhibition of nitrite and cGMP production by AVP was reversed by administration of the specific V1 receptor antagonist [1-(beta-mercapto-beta,beta- cyclopentamethylene propionic acid), 2-(O-methyl)-tyrosine] -Arg8-vasopressin) but not by the oxytocin (OXT) receptor antagonist [d(CH2(5)), TyrMe2, Orn8]-Vasotocin. Administration of the V1 receptor antagonist or OXT receptor antagonist alone did not affect IL-1 beta-stimulated nitrite and cGMP production. Although administration of AVP inhibited IL-1 beta-induced INOS messenger RNA expression, administration of the V1 receptor antagonist but not of the OXT receptor antagonist reversed this inhibition. CONCLUSION: It is suggested that AVP inhibits IL-1 beta-induced NO and cGMP production via the V1 receptor but not via the OXT receptor in VSMC. AVP can cause vascular contraction not only through direct action but also through indirect action by inhibiting NO production under some inflammatory conditions.

Animals↗
PubMed1997

Localization of low-KM cAMP phosphodiesterase in rat nephron segments.

To evaluate the roles of cAMP degradation on hormonal actions in the kidney, we examined the segmental distribution and activities of cAMP-phosphodiesterase (PDE), a key enzyme for cAMP hydrolysis, in dissected segments of the rat nephron and characterized the isozyme compositions with subtype-specific inhibitors. Summary of the nephron distribution of PDE activities showed that cAMP-PDE activities were detected in all nephron segments and the distal convoluted tubules (DCTs) had the highest activity. Both in proximal convoluted tubules (PCTs) and medullary collecting ducts (MCDs), more than 80% of the total cAMP-PDE activities were inhibited by a nonspecific PDE inhibitor, 3-isobutyl-1-methylxanthine (IBMX). In PCTs, rolipram (type-IV PDE inhibitor) was an equally potent inhibitor of IBMX, while 8-methoxymethyl-IBMX (MM-IBMX, type-I PDE inhibitor) and cilostamide (type-III PDE inhibitor) inhibited cAMP-PDE by 35 and 57%, respectively. In MCDs, inhibition by rolipram (40%) was less than that by MM-IBMX (70%) or cilostamide (66%). Rolipram potentiated the parathyroid hormone (PTH)-induced cAMP content in PCTs most effectively. Rolipram and MM-IBMX increased the vasopressin (AVP)-stimulated cAMP content equally in MCDs. Cilostamide had no effect on the cAMP content stimulated by PTH or AVP in PCTs and MCDs. These results indicate that PDE activities were unevenly distributed along the rat nephron and cAMP-PDE was composed of at least three isoforms, namely type I, III and IV in PCTs and MCDs. Among these, type-IV PDE was responsible for hydrolysis of cAMP in PCTs, and type-I and IV PDE were responsible for that in MCDs.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

Cystatin C measurement and its practical use in patients with various renal diseases.

OBJECTIVE: To evaluate the clinical usefulness in terms of estimation for glomerular filtration rate (GFR), we determined the cystatin C levels in the serum and urine of 33 healthy volunteers as well as in the serum and urine of 35 patients with various renal diseases and compared them with those of creatinine. In addition, we evaluated this substance as an indicator of removal rate of low molecular weight protein with high flux membranes in 6 hemodialysis (HD) patients. METHODS: Serum and urinary cystatin C levels were measured by using an enzyme-linked immunosorbent assay (ELISA) method, 24-hour creatinine clearance was used as an indicator of GFR. RESULTS: Reference intervals with 95% ranges are 0.47-1.03 mg/l in the serum from healthy volunteers. There was a significant positive correlation between serum cystatin C and creatinine levels (r = 0.936, p < 0.001) in the patients with various renal diseases. Serum cystatin C and creatinine inversely and logarithmically correlated to creatinine clearance as shown in the following equations: log cystatin C = -0.564 x log creatinine clearance + 1.216 (r = -0.850), log creatinine = -0.678 x log creatinine clearance + 1.449 (r = -0.904). In these equations l/day is the unit used for creatinine clearance, mg/l is the unit used for serum cystatin C. The range for cystatin C is 0.67-6.15 mg/l, 0.66-7.23 mg/dl for creatinine and 8.9-186.3 l/day (6.2-129.4 ml/min) for creatinine clearance. Serum cystatin C levels started to increase over normal range when creatinine clearance fell below 135.9 l/day (94.4 ml/min), while serum creatinine remained within normal ranges. The daily urinary excretion of cystatin C was increased significantly in the group in which creatinine clearance was below 30 l/day (20.8 ml/min) compared to that in which creatinine clearance was higher than in 70 l/day (48.6 ml/min). Fractional clearance of cystatin C increased proportionally and markedly to the decrease of creatinine clearance. In a regular HD condition with high flux membrane, the cystatin C removal rate was 38.7 +/- 1.7%. CONCLUSIONS: These data suggest that combined measurement of cystatin C in the serum and urine is useful to estimate GFR, especially to detect the mild reduction of GFR. Cystatin C measurement can also be used as an indicator of removal rate of low molecular weight protein with different types of high flux membranes in hemodialysis.

Adult↗