Biomedical subjects

H Ikenaga

Publications and source records attributed to H Ikenaga.

At least 37 records · Page 2Linked to original sources

PubMed1996

Contribution of tubuloglomerular feedback to renal arteriolar angiotensin II responsiveness.

The purpose of the present study was to test the hypothesis that a component of the afferent arteriolar vasoconstrictor response to angiotensin II (Ang II) requires an intact tubuloglomerular feedback (TGF) mechanism. Enalaprilat-treated male Sprague-Dawley rats served as tissue donors for study of renal microvascular function using the in vitro blood-perfused juxtamedullary nephron technique. Arteriolar lumen diameter responses to exogenous Ang II were determined before and after TGF blockade (papillectomy or 50 microM furosemide). Before TGF blockage, 10 nM Ang II significantly reduced diameters of both mid-afferent (53 +/- 5%) and efferent (43 +/- 9%) arterioles. TGF blockade did not alter baseline diameter of either arteriole, but significantly blunted the mid-afferent vasoconstriction evoked by 10 nM Ang II (44 +/- 7% inhibition by papillectomy; 43 +/- 10% inhibition by furosemide). Similar behavior was observed at afferent arteriolar sites near the glomerulus; however, efferent arteriolar Ang II responsiveness was not altered by papillectomy. The impact of TGF blockade on afferent arteriolar Ang II responsiveness was most prominent at high peptide concentrations (10 nM), while not significantly influencing the response to 1 nM Ang II. In contrast, the afferent vasoconstrictor effect of norepinephrine was unaffected by papillectomy. These data indicate that the vasoconstrictor influence of exogenous Ang II on afferent, but not efferent, arterioles of intact juxtamedullary nephrons includes both TGF-dependent and TGF-independent components.

Angiotensin II↗

PubMed1996

Basal nitric oxide production curtails arteriolar vasoconstrictor responses to ANG II in rat kidney.

Experiments were performed to test the hypothesis that renal arteriolar vasoconstrictor responses to angiotensin II (ANG II) are curtailed through a mechanism that involves stimulation of endogenous nitric oxide (NO) synthesis. The in vitro blood-perfused juxtamedullary nephron technique was exploited to monitor arteriolar lumen diameter responses to exogenous ANG II before and during treatment with the NO synthase inhibitor N omega-nitro-L-arginine (L-NNA). Under control conditions, 1 nM ANG II reduced afferent and efferent arteriolar diameters by 13 and 11%, respectively. In the presence of L-NNA, 1 nM ANG II decreased afferent diameter by 26% and efferent diameter by 35%. This augmentation could not be attributed to the L-NNA-induced decrease in baseline diameter. L-NNA also augmented vasopressin responses, indicating a lack of agonist specificity in this interaction. ANG II reactivity during L-NNA treatment was not enhanced when tissue NO activity was fixed at basal levels (exposure to 1 microM sodium nitroprusside). These results indicate that endogenous NO modulates the vasoconstrictive impact of ANG II on both afferent and efferent arterioles of juxtamedullary nephrons and that this process does not require stimulation of NO synthesis.

Angiotensin II↗

PubMed1996

Does combined therapy of Ca-channel blocker and angiotensin converting enzyme inhibitor exceed monotherapy in renal protection against hypertensive injury in rats?

Either calcium channel blocker (CCB) or angiotensin converting enzyme inhibitor (ACEi) is used as an antihypertensive agent, and we are recommended to use them in combination to refractory hypertension with evidence dependent on clinical observations. We examined the renal protective effect of the combined therapy with calcium channel blocker (amlodipine) and angiotensin converting enzyme inhibitor (enalapril) against hypertensive renal injury in 5/6 nephrectomized spontaneously hypertensive rats (SHRs) with salt loading, comparing with monotherapy of each drug. Forty males SHRs with 5/6 nephrectomy and salt loading were divided to five groups: group 1 as control (n = 8), group 2 received 0.2 mg/kg/day of amlodipine (n = 8), group 3 received 0.2 mg/kg/day of enalapril (n = 8), group 4 (n = 8) and group 5 (n = 8) that were treated with 0.1 mg/kg/day and 0.2 mg/kg/day of each drug in combination respectively. Either amlodipine or enalapril had remarkable effects on reducing the increases in blood pressure and urinary protein excretion. In histopathological examination, it also suppressed renal injury significantly. Additional significant effect of combined therapy was not observed in blood pressure and urinary protein. There were not remarkable, additional effects of the combination of CCB and ACEi on protecting the remnant kidney in 5/6 nephrectomized SHRs fed a high-salt diet, possibly because sodium retention was not alleviated by the combination.

Amlodipine↗

PubMed1996

Sodium balance and hypertension in obese and fatty rats.

To investigate the role of sodium in obesity induced hypertension, Wistar fatty rats (WFR) were employed. This rat has the following characteristics: (1) hyperglycemia, (2) hyperinsulinemia, and (3) hypertriglycemia. Four percent sodium chloride with constant amount of food intake was administered to these rats from 8 to 16 weeks. During this period, body wt, food intake, water consumption, urine volume, systolic blood pressure, urinary excretion of sodium and potassium, urinary albumin excretion, plasma sodium and potassium, and plasma glucose and immunoreactive insulin (IRI) were measured before, and twice more during eight weeks. No remarkable changes were observed in plasma glucose level during these periods between the two groups. On the other hand, in group 1 IRI significantly increased compared with group 2. Mean blood pressure was increased from 110 +/- 5 to 130 +/- 8 mm Hg (P < 0.01). To ascertain whether this salt sensitivity relates to the abnormalities in pressure-natriuresis responses, the pressure-natriuresis (P-N) was characterized. The P-N curve in WFR was shifted to the right and its slope was flattened compared to its control Wistar lean rats. In conclusion, an excess of dietary sodium intake may contribute to an elevation of blood pressure in Wistar fatty rat with hyperglycemia and hyperinsulinemia. This salt sensitivity may change the abnormal pressure-natriuresis responses.

Animals↗

PubMed1995

Cloning and expression of a porcine UDP-GalNAc: polypeptide N-acetylgalactosaminyl transferase.

By employing a bovine UDP-N-acetylgalactosamine: polypeptide N-acetylgalactosaminyl transferase (O-GalNAc transferase) cDNA as a probe, we isolated four overlapping cDNAs from a porcine lung cDNA library. Both the nucleotide sequence of the porcine cDNA and the predicted primary structure of the protein (559 amino acids) proved to be very similar to those of the bovine enzyme (95% and 99% identity, respectively). Transient expression of the clone in COS-7 cells, followed by enzymatic activity assays, demonstrated that this cDNA sequence encodes a porcine O-GalNAc transferase. The intracellular O-GalNAc transferase activity was increased approximately 100-fold by transfecting cells with the porcine cDNA.

Amino Acid Sequence↗

PubMed1995

Renal responses to angiotensin receptor antagonist and angiotensin-converting enzyme inhibitor in partially nephrectomized spontaneously hypertensive rats.

To investigate the role of the renin-angiotensin system (RAS) on nephrosclerosis in salt-loaded, partially nephrectomized spontaneously hypertensive rats (SHR), we evaluated the effects of angiotensin II (ANGII) blockade on the progression of nephrosclerosis with an angiotensin type 1 receptor (AT1rec) antagonist [TCV-116 (TCV)] and an angiotensin-converting enzyme (ACE) inhibitor (enalapril) at the doses equivalent in reducing systemic blood pressure (BP). SHR were five/sixths nephrectomized and were fed a high-salt diet. In addition to being significantly preventive against an increase in systolic BP, both TCV and enalapril significantly attenuated the increases in proteinuria and the renal histopathological alterations. Transcription of AT1rec mRNA in the remnant kidney was enhanced with the progression of nephrosclerosis, but was inhibited by TCV as well as enalapril. In these aspects, there were no apparent differences between effects of TCV and enalapril. The RAS system plays an important role in nephrosclerosis in partially nephrectomized SHR despite a high-salt diet, and direct ANGII blockade certainly protected the kidney against hypertensive injury in this model.

Angiotensin Receptor Antagonists↗

PubMed1995

[The clinical significance of the ratio in FSH/LH of human menopausal gonadotropins in a programmed stimulation regimen for IVF-ET].

Human menopausal Gonadotropin (hMG) has been used in controlled ovarian hyperstimulation (COH) protocol for IVF-ET. We investigated three hMG preparations with different FSH/LH ratios to determine their clinical effectiveness in a programmed stimulation regimen for IVF-ET. Eighty-four IVF-ET candidates at Toho University Hospital received injections of an hMG preparation containing a 3:1 ratio of FSH/LH: Group A, 36 patients received hMG at an FSH/LH 1 : 1 ratio: Group B, and 20 patients receive pure FSH : group C. All received injections of 300IU hMG daily for 7 days according to our COH protocol (=7-day schedule). Analysis determined the serum levels of E2, number of mature follicles, number of retrieved oocytes, fertilization rate, cleavage rate, number of transferred embryos and pregnancy rate. The results were as follows: 1. The serum E2 level was higher in Group A than in Group C with significant differences. 2. The oocyte retrieval rate was significantly higher in Group A. 3. The rate of equally cleaved eggs was significantly higher in Group A. 4. The pregnancy rate was significantly higher in Group A. In conclusion, an hMG preparation containing a 3 : 1 FSH/LH ratio was most suitable in our COH protocol.

Drug Administration Schedule↗

PubMed1994

Metabolic engineering for production of beta-carotene and lycopene in Saccharomyces cerevisiae.

We have engineered a conventional yeast, Saccharomyces cerevisiae, to confer a novel biosynthetic pathway for the production of beta-carotene and lycopene by introducing the bacterial carotenoid biosynthesis genes, which are individually surrounded by the promoters and terminators derived from S. cerevisiae. beta-Carotene and lycopene accumulated in the cells of this yeast, which was considered to be a result of the carbon flow for the ergosterol biosynthetic pathway being partially directed to the pathway for the carotenoid production.

Carotenoids↗

PubMed1994

Elution profiles and molecular weights of placental cystine aminopeptidase in animals.

Gel filtration was performed for cystine aminopeptidase (CAP) [EC 3.4.11.3] on full term placental extracts from human, cynomolgus monkey, dog, goat, pig and horse. The enzymatic profiles of CAP were examined and compared with that of CAP in pregnancy plasma on the basis of inhibitory effects. Elution profiles of placental extracts exhibited 2 CAP activity peaks in human and pig, 3 peaks in cynomolgus monkey, dog and goat, and 4 peaks in horse. The molecular weights of placental CAP that showed identical inhibitory effects to that of pregnancy plasma CAP were estimated to be approximately 325,000 in human, 350,000 in the cynomolgus monkey, 140,000 in the dog, 140,000 in the goat, 128,000 in the pig, and 115,000 in the horse. These molecular weights tended to decrease in accordance with the increase of barrier layers present between maternal blood and placental syncytiotrophoblasts in which CAP is synthesized.

Animals↗

PubMed1994

Effects of a calcium channel blocker, nicardipine, on pressure-natriuresis in Dahl salt-sensitive rats.

The effects of a calcium channel blocker, nicardipine, on pressure-natriuresis responses were studied in Dahl salt sensitive (DS) and resistant (DR) rats. Differences in the neural and endocrine background were minimized by renal denervation and by holding plasma vasopressin, aldosterone, corticosterone, and norepinephrine levels constant by intravenous infusion. The renal plasma flow (RPF) and glomerular filtration rate (GFR) of DS rats were disautoregulated in the low renal perfusion pressure range, while those of DR rats were autoregulated. Administration of nicardipine (0.3 microgram/kg/min) into the renal artery significantly increased RPF and GFR and abolished the autoregulation in both strains of rats. Nicardipine also sharpened the pressure-natriuresis responses in both strains without changes in fractional excretion of sodium. These findings suggest that nicardipine increased GFR and thereby improved the pressure-natriuresis responses of DS rats.

Animals↗

PubMed1994

Nonpeptide angiotensin II type 1 receptor antagonist prevents nephrosclerosis in hypertensive rats.

Angiotensin II (AII) appears essential in remnant kidney models of renal injury in rats, and renal injury was reduced by angiotensin-converting enzyme inhibitor (ACEI). To determine whether this is due to AII blockade or other actions of ACEI, we studied a nonpeptide AII type 1 receptor antagonist and an ACEI in partially nephrectomised spontaneously hypertensive rats (SHR). Thirty SHR underwent surgery and were divided into three equal groups: Control, TCV (0.5 mg/kg/day TCV-116), and CAP (30 mg/kg/day captopril). All SHR received a 5%-NaCl diet. Systolic blood pressure (SBP) and urinary protein were measured at 2-week intervals. Serum total protein, albumin, urea nitrogen, and creatinine were determined at week 8. Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured at weeks 4 and 8. Renal injury was evaluated histopathologically. TCV and CAP reduced SBP at week 2 and proteinuria at week 8. GFR and RBF fell in all groups, but decreases were not significant in treated SHR and histopathological changes were significantly ameliorated. All blockade by TCV or CAP reduces renal injury in salt-loaded SHR with partial renal ablation. AII is essential in remnant kidney models of renal injury, and AII blockade is essential in renal protection by ACEI.

Angiotensin Receptor Antagonists↗

PubMed1993

Zymobacter palmae gen. nov., sp. nov., a new ethanol-fermenting peritrichous bacterium isolated from palm sap.

Zymobacter palmae gen. nov., sp. nov. was proposed for a new ethanol-fermenting bacterium that was isolated from palm sap in Okinawa Prefecture, Japan. The bacterium is gram-negative, facultatively anaerobic, catalase-positive, oxidase-negative, nonsporeforming and peritrichously flagellated. It requires nicotinic acid for growth. It ferments hexoses, alpha-linked di- and tri-saccharides, and sugar alcohols (fructose, galactose, glucose, mannose, maltose, melibiose, saccharose, raffinose, mannitol and sorbitol). Fifteen percent of maltose in broth medium is effectively fermented, whereas glucose with a concentration higher than 10% delayed growth initiation and decreased growth rates. Maltose is fermented to produce ethanol and CO2 with a trace amount of acids. Approximately 2 mol of ethanol are produced from 1 mol moiety of hexose of maltose. The organism possesses ubiquinone-9. The G + C content of the DNA is 55.8 +/- 0.4 mol%. Major cellular fatty acids were palmitic and oleic acids and cyclopropanic acid of C19:0. Characteristic hydroxylated acid was 3-hydroxy dodecanoic acid. The bacterium is distinct from other ethanol-fermenting bacteria belonging to the genera Zymomonas Kluyver and van Niel 1936 and Saccharobacter Yaping et al. 1990 with respect to chemotaxonomic and other phenotypic characters to warrant to compose a new genus and a new species. The type strain is strain T109 (= IAM 14233).

Base Sequence↗

PubMed1993

Role of NO on pressure-natriuresis in Wistar-Kyoto and spontaneously hypertensive rats.

We investigated the role of the endothelium-derived relaxing factor nitric oxide (NO) on pressure-natriuresis in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) using in vivo perfusion studies. Differences in the neural and hormonal background to the kidney were minimized by renal denervation and by holding plasma vasopressin, aldosterone, corticosterone, and norepinephrine levels constant by intravenous infusion. In WKY, elevation of renal perfusion pressure (RPP) from 115 to 157 mm Hg increased urinary sodium excretion 4.5 to 14.8 microEq/min/g kidney wt, and the slope of its linear regression was 0.21 microEq/min/g kidney wt/mm Hg. Infusion of an inhibitor of NO synthase, L-NMMA (1 mg/min/kg), lowered this slope (P < 0.05) but L-arginine (3 mg/min/kg) did not change it. By contrast, the impaired pressure-natriuresis response of SHR was ameliorated by L-arginine (slope: 0.08 to 0.16; P < 0.05), while L-NMMA did not blunt it further. GFR and renal plasma flow (RPF) were well autoregulated in both strains, but L-NMMA lowered RPF significantly (SHR: from 4.2 to 2.6 ml/min/g kidney wt; WKY: 4.5 to 2.5 ml/min/g kidney wt). Moreover, when infused simultaneously, all these individual effects of L-NMMA and L-arginine were nullified. These results suggest that NO plays an important role in the pressure-natriuresis mechanism.

Amino Acid Oxidoreductases↗

PubMed1993

Enzymuria in non-insulin-dependent diabetic patients: signs of tubular cell dysfunction.

1. To evaluate tubular damage in diabetic patients, we measured the 24 h urinary excretion of five enzymes (N-acetyl-beta-D-glucosaminidase, gamma-glutamyl transpeptidase, dipeptidyl aminopeptidase IV, alanine aminopeptidase and alkaline phosphatase) that originate in renal proximal tubular cells. 2. Studies were performed on 118 non-insulin-dependent diabetic patients, 59 non-diabetic patients with chronic renal disease and 47 normal control subjects. First, the correlation between renal function, glycaemic control and urinary enzyme excretion was investigated. Secondly, the subjects were treated by controlled diet therapy to assess the effects of better glycaemic control on urinary enzyme excretion. 3. Regardless of a diabetic or non-diabetic cause of renal dysfunction, all of the five enzymes showed abnormal urinary excretion in patients with renal insufficiency (serum creatinine concentration > 2.0 mg/dl). In diabetic patients, however, an increase in N-acetyl-beta-D-glucosaminidase excretion and a decrease in gamma-glutamyl transpeptidase excretion were noted even in those who had no signs of renal dysfunction, including microalbuminuria. Moreover, the excretion of these two enzymes had a higher degree of correlation with glycaemic control and renal function than did that of the other three enzymes. Multiple regression analysis revealed that excretion of N-acetyl-beta-D-glucosaminidase is best correlated with urinary protein (r2 = 0.35), whereas excretion of gamma-glutamyl transpeptidase is closely associated with glomerular filtration rate (r2 = 0.33). 4. In diabetic patients, diet therapy improved glycaemic control but had no effects on renal function, microalbumin excretion and beta 2-microglobulin excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗

PubMed1993

Functional expression of the Erwinia uredovora carotenoid biosynthesis gene crtl in transgenic plants showing an increase of beta-carotene biosynthesis activity and resistance to the bleaching herbicide norflurazon.

Among the enzymes involved in carotenoid biosynthesis, phytoene desaturase is considered to be a rate-limiting enzyme in this pathway and is also the target of many bleaching herbicides. This enzyme shows diversity concerning its function and amino acid homology among various organisms. The phytoene desaturase gene crtl of Erwinia uredovora was expressed, the 5'-region of which was fused to the sequence for the transit peptide of a pea Rubisco small subunit, in tobacco plants under the control of the CaMV 35S promoter. This chimeric gene product was targeted into chloroplasts and processed in the transgenic plants. The production and processing of the corresponding protein could be demonstrated by Western blotting. Immunogold localization showed that the location of the gene product Crtl was preferentially in the thylakoids. A radioactive labeling study using the leaves demonstrated enhanced activity for the synthesis of beta-carotene. In addition, the transgenic tobacco acquired elevated resistance to the bleaching herbicide norflurazon.

Amino Acid Sequence↗

PubMed1993

Placental and plasma cystine aminopeptidase in pregnant animals.

The placental and plasma cystine aminopeptidase (CAP) in pregnant animals was examined on stability after the treatment with L-methionine, ethylene diamine tetra-acetic acid (EDTA) and heat. Inhibitory effects of these treatments on enzyme activities were different among CAPs from the animal species, however, significant correlation in those effects between placental and plasma CAPs was observed. These results suggested that plasma CAP might reflect placental CAP and seemed to be available for estimating maternal gestational conditions.

Animals↗

PubMed1993

Effects of sodium and chloride ions on blood pressure in deoxycorticosterone acetate-treated rats.

The effects of sodium (Na+) and chloride ions (Cl-) on blood pressure were studied in rats treated with deoxycorticosterone acetate (DOCA). Four groups were prepared, each consisting of male Wistar rats that underwent heminephrectomy and administration of DOCA: the control group was maintained with tap water, the NaCl group with tap water containing 1% sodium chloride, the NaCit group with tap water containing 1.67% sodium citrate (including an equivalent dose of Na+ to 1% NaCl), and the ChoCl group with tap water containing 1.15% choline chloride (including an equivalent dose of Cl- to 1% NaCl). The time-course of systolic blood pressure showed only slight change in blood pressure in the control and ChoCl groups, and in the NaCl and NaCit groups. The rotational correlation time, an index of the fluidity of erythrocyte membrane, with spin-labeling of 16-doxyl-stearic acid, was significantly (p < 0.05) higher in the NaCl and NaCit groups than in the control group, indicating an increase in the membrane fluidity, i.e., membrane fragility. The sodium, potassium ions-activated adenosine triphosphatase (Na+,K(+)-ATPase) activity of the erythrocyte membrane was decreased to 22% (P < 0.01) and 24% (P < 0.01) in the NaCl and NaCit groups, respectively, compared with the control groups; this activity was decreased to 43% in the ChoCl group (P < 0.05). The Ca(2+)-ATPase activity showed similar changes. In contrast, there were no marked differences in the erythrocyte electrolyte level between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Increases in NO2-/NO3- excretion in the urine as an indicator of the release of endothelium-derived relaxing factor during elevation of blood pressure.

1. Under hormonally constant conditions, the effects of a sudden increase in blood pressure on the release of endothelium-derived relaxing factor were evaluated by measuring urinary excretion of NO2-/NO3- in rats with renal denervation. 2. Elevation of blood pressure from 136 +/- 2 to 153 +/- 3 mmHg by an aortic clamp below the renal arteries induced a significant increase in urinary excretion of NO2-/NO3- from 76.6 +/- 4.2 x 10(2) to 108.1 +/- 8.3 x 10(2) pmol min-1 g-1 kidney weight (P less than 0.05). 3. Infusion of NG-monomethyl-L-arginine (1 mg min-1 kg-1) without an aortic clamp raised mean blood pressure to a similar level; however, urinary excretion of NO2-/NO3- was decreased significantly. 4. During infusion of NG-monomethyl-L-arginine, aortic occlusion caused a significant increase in blood pressure without any changes in NO2-/NO3- excretion in the urine. 5. These results suggest that the formation of NO, an indicator of endothelium-derived relaxing factor release, was increased by mechanical pressure elevation without apparent changes in hormonal and neural factors.

Animals↗