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Biomedical subjects

Sadayoshi Ito

Publications and source records attributed to Sadayoshi Ito.

At least 73 records · Page 4Linked to original sources
PubMed2004

[RAS blockade].

Angiotensin II (AII), the biologically active component of renin-angiotensin system (RAS), acts through two receptor subtypes, the AT1 and AT2 receptor. All classic physiological effects of AII, such as vasoconstriction, aldosterone and vasopressin release, sodium and water retention and sympathetic facilitation, are mediated by the AT1 receptor. The majority of pilot studies demonstrated the renoprotective effect of RAS blockers via antihypertensive, antiproteinuric, antifibrotic action. In order to establish whether RAS blocker causes antiproteinuric effects or long-term renoprotection in the non-diabetic nephrotic disease, larger prospective, randomized controlled trials are required in the future.

Angiotensin II↗
PubMed2004

[Pheochromocytoma].

Explore the source record for details and available documents.

Adrenal Gland Neoplasms↗
PubMed2004

[Role of androgens in the renal production of 20-hydroxyeicosatetraenoic acid in spontaneously hypertensive rats].

The role of androgens in the production of 20-hydroxyeicosatetraenoic acid (20-HETE) was determined in the kidney of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The renal production of 20-HETE and blood pressure were higher in males than in females at 9 weeks of age. The renal production of 20-HETE was significantly greater in male SHR than in male WKY, whereas it was significantly lower in female SHR than in female WKY. The differences in the renal production of 20-HETE were consistent with the cytochrome P-450 4A protein levels. Plasma free-testosterone levels in male SHR were twice as high as those in male WKY. Castration and treatment with the androgen receptor antagonist, flutamide, reduced blood pressure, the renal production of 20-HETE, and P-450 4A protein levels in both strains. The renal production of 20-HETE was significantly lower in castrated SHR than in castrated WKY. These results indicate that the renal production of 20-HETE and the expression of P-450 4A have gender and strain-differences, and high levels of plasma androgens induce the expression of P-450 4A and the production of 20-HETE in the kidney of male SHR. The androgen-induced production of 20-HETE may be associated with hypertension in male SHR.

Androgens↗
PubMed2003

Endothelium-derived nitric oxide modulates vascular action of aldosterone in renal arteriole.

We have recently demonstrated that aldosterone causes nongenomic vasoconstriction by activating phospholipase C (PLC) in the preglomerular afferent arteriole (Af-Art). In the present study, we tested the hypothesis that endothelium modulates this vasoconstrictor action by releasing nitric oxide (NO). In addition, to study the post-PLC mechanism, we examined possible contributions of phosphoinositol hydrolysis products. Rabbit Af-Arts were microperfused at 60 mm Hg in vitro, and increasing doses of aldosterone (10(-10) to 10(-8) mol/L) were added to the bath and lumen. Aldosterone caused dose-dependent vasoconstriction (within 10 minutes); significant (P<0.01) constriction was observed from 5x10(-9) mol/L, and at 10(-8) mol/L, intraluminal diameter decreased by 29%+/-3% (n=9). Disrupting the endothelium augmented vasoconstriction; significant constriction was observed from 10(-10) mol/L, and at 10(-8) mol/L, the diameter decreased by 38%+/-2% (n=6). NO synthesis inhibition reproduced this augmentation (n=7). Pretreatment with chelerythrine (10(-6) mol/L), a protein kinase C (PKC) inhibitor, slightly attenuated the constriction; aldosterone at 10(-8) mol/L now decreased the diameter by 18%+/-3% (n=7). However, in Af-Arts treated with thapsigargin (10(-6) mol/L) or dantrolene (3x10(-5) mol/L), which blocks inositol 1,4,5-triphosphate (IP3)-induced intracellular calcium release, aldosterone at 10(-8) mol/L decreased the diameter by only 9%+/-1% (n=6) or 9%+/-2% (n=5), respectively. These results demonstrate that in the Af-Art endothelium-derived NO modulates vasoconstrictor actions of aldosterone that are mediated by the activation of both IP3 and PKC pathways. Such vasoconstrictor actions of aldosterone may contribute to the development or aggravation of hypertension by elevating renal vascular resistance in cardiovascular diseases associated with endothelium dysfunction.

Aldosterone↗
PubMed2003

Activation of peroxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletal muscle and attenuates metabolic syndrome.

In this study, we defined the role of peroxisome proliferator-activated receptor beta/delta (PPARdelta) in metabolic homeostasis by using subtype selective agonists. Analysis of rat L6 myotubes treated with the PPARdelta subtype-selective agonist, GW501516, by the Affymetrix oligonucleotide microarrays revealed that PPARdelta controls fatty acid oxidation by regulating genes involved in fatty acid transport, beta-oxidation, and mitochondrial respiration. Similar PPARdelta-mediated gene activation was observed in the skeletal muscle of GW501516-treated mice. Accordingly, GW501516 treatment induced fatty acid beta-oxidation in L6 myotubes as well as in mouse skeletal muscles. Administration of GW501516 to mice fed a high-fat diet ameliorated diet-induced obesity and insulin resistance, an effect accompanied by enhanced metabolic rate and fatty acid beta-oxidation, proliferation of mitochondria, and a marked reduction of lipid droplets in skeletal muscles. Despite a modest body weight change relative to vehicle-treated mice, GW501516 treatment also markedly improved diabetes as revealed by the decrease in plasma glucose and blood insulin levels in genetically obese ob/ob mice. These data suggest that PPARdelta is pivotal to control the program for fatty acid oxidation in the skeletal muscle, thereby ameliorating obesity and insulin resistance through its activation in obese animals.

Animals↗
PubMed2003

Identification and characterization of novel rat and human gonad-specific organic anion transporters.

We have isolated three novel organic anion transporter cDNAs designated rat GST-1 (gonad-specific transporter), rat GST-2, and human GST, expressed at high levels in the testis. Rat GST-1, GST-2, and human GST consist of 748, 702, and 719 amino acids, respectively, and all molecules possess the 12 predicted transmembrane domains, which is a common structure of organic anion transporters. Northern blot analyses and in situ hybridization revealed that both of the rat molecules are highly expressed in the testis, especially in Sertoli cells, spermatogonia, and Leydig cells. Weak signals are also detected in the epididymis and ovary in adult rat. The exclusive expression of human GST mRNA in the testis was confirmed by RT-PCR. The pharmacological experiments of Xenopus laevis oocytes injected with the respective rat GST-1- and GST-2-cRNAs revealed that both rat GST-1 and GST-2 transport taurocholic acid, dehydroepiandrosterone sulfate, and T4 with Michaelis-Menten kinetics (taurocholic acid, Km = 8.9 and 2.5 microm, dehydroepiandrosterone sulfate, Km = 25.5 and 21.microm, and T4, Km = 6.4 and 5.8 for rat GST-1 and GST-2, respectively). T3 was also transported by rat GST-1 and GST-2. These data suggest that rat GST-1 and GST-2 might be one of the molecular entities responsible for transporting dehydroepiandrosterone sulfate and thyroid hormones involved in the regulation of sex steroid transportation and spermatogenesis in the gonad.

Amino Acid Sequence↗
PubMed2003

The involvement of advanced glycation endproducts (AGEs) in renal injury of diabetic glomerulosclerosis: association with phenotypic change in renal cells and infiltration of immune cells.

BACKGROUND: Glycation of proteins is regarded as one of the major causes of the progression of diabetic nephropathy (DN) and of the phenotypic changes in glomerular mesangial cells (MC) and the cellular infiltration that occurs in MC from DN. It thus is very important to study the interrelationships and interaction between these causes. METHODS: The localization of advanced glycation endproducts (AGEs), cytoskeletal proteins, and immune cell infiltration was evaluated by immunohistochemical study in patients with DN. RESULTS: N(Epsilon)-(carboxymethyl)lysine (CML), Alpha-smooth muscle actin (SMA), and low-molecular-weight caldesmon (L-CLD) were localized in the mesangial area in DN. The intensity of mesangial SMA and L-CLD expression was significantly correlated with the index of diabetic glomerulosclerosis (IDGS), while the expression of pentosidine was correlated with the IDGS and with 24-h urinary protein. Pentosidine was localized in glomerular basement membrane (GBM) only in DN and had a significant correlation with the mesangial expression of SMA and L-CLD. Pyrraline deposition on the tubular basement membrane, and the expression of SMA and L-CLD, and the infiltration of immune cells were observed in interstitial areas in DN. The intensity of L-CLD expression had a close relationship with pyrraline deposition and immune cell infiltration. The expression of SMA and L-CLD in interstitial areas was significantly correlated with the percent interstitial volume. CONCLUSIONS: AGEs are involved in renal injury in DN, and their effect is, at least in part, exercised via phenotypic changes in intrinsic renal cells and by the infiltration of immune cells.

Actins↗
PubMed2003

The influence of one-year treatment by angiotensin converting enzyme inhibitor on baroreflex sensitivity and flow-mediated vasodilation of the brachial artery in essential hypertension--comparison with calcium channel blockers.

BACKGROUND: Both baroreflex sensitivity and flow-mediated vasodilator function have been recognized to have prognostic significance in cardiovascular diseases. Long-term antihypertensive treatment effects on these parameters, however, remain unclear. SUBJECTS AND METHODS: We examined the effects of long-term treatment by angiotensin converting enzyme inhibitors (ACEI) orcalcium channel blockers (CCB) on baroreflex and flow-mediated vasodilator function in patients with essential hypertension (EH). We recruited 36 patients aged 56 +/- 11 years, with systolic blood pressure > or = 160 mmHg and/or diastolic blood pressure > or = 95 mmHg. Patients were assigned either to treatment by long-acting ACEI (n = 12) or CCB (n = 24). All patients were followed for 12 months. Optimal BP was achieved by two optional increases in treatment: dose-doubling of the primary drug during the first three months and the addition of diuretics or beta-blockers thereafter. Target blood pressure was 140/90 mmHg or a fall > or = 20/10 mmHg. Baroreflex sensitivity was examined by spectral analysis of blood pressure and RR interval variabilities before treatment and after 3 and 12 months of treatment. The flow-mediated vasodilator function was determined before and 12 months after treatment by measuring the change in brachial artery diameter during increases in flow induced by reactive hyperemia. RESULTS: Baseline blood pressures were similar between the ACEI and CCB groups (172 +/- 5/103 +/- 2 vs. 172 +/- 4/101 +/- 3 mmHg). Blood pressures after 3 and 12 months of treatment also did not differ between the ACEI and CCB groups (149 +/- 4/91 +/- 2 vs. 145 +/- 2/85 +/- 2 mmHg, and 133 +/- 5/84 +/- 2 vs. 133 +/- 2/81 +/- 2 mmHg, respectively). Baseline baroreflex sensitivity was similar between the groups (6.7 +/- 0.8 vs. 5.9 +/- 0.6 msec/mmHg). This parameter remained unchanged at three months but increased after 12 months of treatment in both the ACEI (9.5 +/- 1.6 msec/mmHg, p = 0.05) and CCB (9.1 +/- 1.2 msec/mmHg, p = 0.006) groups. Percent increases in brachial arterial diameter and flow during reactive hyperemia increased in the group treated with ACEI (12.4 +/- 3.5 vs. 25.8 +/- 6.3% and 618 +/- 72 vs. 953 +/- 166, p < 0.05 for both) but both parameters remained unchanged in the group treated with CCB. CONCLUSION: These data suggest that long-term blood pressure control with modem antihypertensive drugs improves baroreflex function. Treatment with ACEI may be more favorable for flow-mediated vasodilator function than treatment with CCB.

Aged↗
PubMed2003

Nongenomic vascular action of aldosterone in the glomerular microcirculation.

Aldosterone (Aldo) accelerates hypertension, proteinuria, and glomerulosclerosis in animal models of malignant hypertension or chronic renal failure. Aldo may exert these deleterious renal effects by elevating renal vascular resistance and glomerular capillary pressure. To test this possibility, directly examined were the action of Aldo on the afferent (Af) and efferent (Ef) arterioles (Arts). Examined were the effect of Aldo added to both the bath and lumen on the intraluminal diameter (measured at the most responsive point) of rabbits. Aldo caused dose-dependent constriction in both arterioles with a higher sensitivity in Ef-Arts. Vasoconstrictor action of Aldo was not affected by a mineralocorticoid receptor antagonist spironolactone and was reproduced by membrane-impermeable albumin-conjugated Aldo, suggesting that the vasoconstrictor actions are nongenomic. Pretreatment with neomycin (a specific inhibitor of phospholipase C) abolished the vasoconstrictor action of Aldo in both arterioles. In addition, the vasoconstrictor action of Aldo on Af-Arts was inhibited by both nifedipine and efonidipine, whereas that on Ef-Arts was inhibited by efonidipine but not nifedipine. The results demonstrate that Aldo causes nongenomic vasoconstriction by activating phospholipase C with a subsequent calcium mobilization thorough L- or T-type voltage-dependent calcium channels in Af- or Ef-Arts, respectively. These vasoconstrictor actions on the glomerular microcirculation may play an important role in the pathophysiology and progression of renal diseases by elevating renal vascular resistance and glomerular capillary pressure.

Aldosterone↗
PubMed2003

Molecular characterization of human and rat organic anion transporter OATP-D.

We have isolated and characterized a novel human and rat organic anion transporter subtype, OATP-D. The isolated cDNA from human brain encodes a polypeptide of 710 amino acids (Mr 76,534) with 12 predicted transmembrane domains. The rat clone encodes 710 amino acids (Mr 76,821) with 97.6% amino acid sequence homology with human OATP-D. Human and rat OATP-D have moderate amino acid sequence homology with LST-l/rlst-1, the rat oatp family, the prostaglandin transporter, and moatl/MOAT1/KIAA0880/OATP-B. Phylogenetic tree analysis revealed that OATP-D is branched in a different position from all known organic anion transporters. OATP-D transports prostaglandin E1 (Km 48.5 nM), prostaglandin E2 (Km 55.5 nM), and prostaglandin F2,, suggesting that, functionally, OATP-D encodes a protein that has similar characteristics to those of the prostaglandin transporter. Rat OATP-D also transports prostaglandins. The expression pattern of OATP-D mRNA was abundant mainly in the heart, testis, brain, and some cancer cells. Immunohistochemical analysis further revealed that rat OATP-D is widely expressed in the vascular, renal, and reproductive system at the protein level. These results suggest that OATP-D plays an important role in translocating prostaglandins in specialized tissues and cells.

Alprostadil↗
PubMed2003

Urinary concentration defect and limited expression of sodium cotransporter, rBSC1, in a rat model of chronic renal failure.

BACKGROUND: Renal urinary concentration is associated with enhanced expression of sodium cotransporter (rBSC1) in thick ascending limb of Henle. Overexpression of rBSC1 was reported recently in hypertrophied nephrons after unilateral nephrectomy (UNX) and in kidney isografts. Since urinary concentration defect and hypertrophy of residual nephrons are major manifestations of chronic renal failure (CRF), we investigated the rBSC1 signals for RNA and protein in a rat model of CRF. METHODS: Rats underwent 5/6 nephrectomy and examined 8 weeks after operation. rBSC1 mRNA was examined by competitive PCR and in situ hybridization, and rBSC1 protein signals by western blotting and immunohistochemistry. Rats that underwent sham-operation, UNX, or 5/6 nephrectomy followed by a 3-week recovery period (acute renal failure), were used as control. Water intake was restricted for 24 h in subgroups of control and CRF rats. RESULTS: Microscopic examination showed hypertrophy of residual nephrons in both UNX and CRF rats. Signals for rBSC1 mRNA and protein were enhanced at basal condition only in rats with UNX. Under basal conditions, CRF rats demonstrated low urinary osmolality in spite of high plasma arginine vasopressin levels. Water restriction resulted in increased signals for rBSC1 mRNA and protein and concentration of urine in sham-operated rats, but such increases were absent and urinary concentration was incomplete in CRF rats. CONCLUSIONS: Compensatory overexpression and upregulation of rBSC1 expression in response to dehydration are both absent in CRF rats. These limitations are thought to be the underlying mechanisms of urinary concentrating defect seen in CRF.

Animals↗
PubMed2003

Immunolocalization of nuclear transcription factors, DAX-1 and COUP-TF II, in the normal human ovary: correlation with adrenal 4 binding protein/steroidogenic factor-1 immunolocalization during the menstrual cycle.

Steroid synthesis in the human ovary is regulated by the temporal and spatial expression of enzymes involved in each step of ovarian steroidogenesis. Recent studies have demonstrated that DAX-1 and COUP-TFII negatively regulate adrenal 4 binding protein (Ad4BP)/steroidogenic factor-1 (SF-1)-dependent transcription of steroidogenic enzymes in experimental animals. In this study the expression patterns of these proteins in human normal ovaries were examined using immunohistochemistry and compared with those of steroidogenic enzymes. In the ovarian follicle and corpora lutea, immunoreactive DAX-1 protein was detected predominantly in granulosa cells, whereas COUP-TFII was identified in thecal cells. In granulosa cells, both immunoreactive DAX-1 and Ad4BP/SF-1 protein expression increased after the preantral follicular stage. DAX-1 immunoreactivity was relatively high compared with that of Ad4BP/SF-1 in all follicular stages from premordial to nondominant. The increase in expression of Ad4BP/SF-1 immunoreactivity between follicles in the preantral and dominant stages of follicular development was greater than that in DAX-1 expression. In thecal cells, immunoreactive COUP-TFII was consistently elevated throughout the menstrual cycle, whereas Ad4BP/SF-1 immunoreactivity increased according to the development of the follicle. These results indicated that DAX-1 and COUP-TFII may play a role in the modulation of Ad4BP/SF-1-dependent transcription of steroidogenic enzymes in different cell types and follicular stages in normal cycling human ovaries.

Adult↗
PubMed2003

Plasma BNP levels in the treatment of type 2 diabetes with pioglitazone.

We monitored the change in plasma ANP and BNP levels (as markers for left ventricular dysfunction (LVD)) in DM2 patients treated with pioglitazone (Pio) for 4 weeks. Thirty DM2 patients with no sign of heart failure were treated with Pio (15 mg/day), and their plasma ANP (normal levels <or=43 pg/ml) and BNP levels (normal levels <or=18.4 pg/ml) were examined. We also examined those levels in no drug-treatment group (n = 10) as well as buformine treatment group (n = 10). Among these groups, there were no significant differences in clinical profiles related to DM control. Pio treatment was terminated when BNP (above 100 pg/ml) and ANP levels (above 50 pg/ml) suggested the left ventricular dysfunction (LVD). The patients (n = 12) whose BNP levels reached to the LVD-positive levels showed the basal BNP levels above the normal upper limit (18 pg/ml), while the rest of subjects (n = 18) whose basal BNP levels within normal limits did not showed the LVD-positive levels in the Pio-treatment. On the other hand basal ANP levels did not predict the development to LVD. In conclusion, BNP levels are suggested to be a good marker of Pio-induced LVD, and the Pio treatment of DM2 patients with BNP levels above the normal limit should be carefully carried out by monitoring BNP levels.

Aged↗