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Biomedical subjects

K Hiwada

Publications and source records attributed to K Hiwada.

At least 343 records · Page 19Linked to original sources
PubMed1985

Effects of renal denervation on renin release induced by intracerebroventricular administration of biological active peptides in conscious rats.

Experiments were performed to determine whether the renal nerve mediates the renin release induced by intracerebroventricular administration of angiotensin II (ANG II), bradykinin (BK), leucine-enkephalin (Leu-ENK) and neurotensin (NT). In sham-operated rats, both ANG II and NT suppressed plasma renin activity (PRA), BK did not affect PRA, and Leu-ENK increased PRA. Renal denervation abolished the increase in PRA by Leu-ENK. Suppression of PRA by ANG II was attenuated in denervated rats. Renal denervation did not influence the renin release by BK or NT. These results suggest that the renal nerve plays an important role in elevating PRA after central stimulation by Leu-ENK. Although suppression of PRA is mainly mediated by mechanisms other than the renal nerve, the renal nerve partially participates in suppression of PRA by ANG II.

Angiotensin II↗
PubMed1985

A radioimmunoassay for the measurement of aminopeptidase (microsomal) in human serum.

A radioimmunoassay for the measurement of aminopeptidase (microsomal) (AP) in human serum was developed by using antiserum to human kidney AP. AP purified from kidney and AP present in normal serum and in serum from a patient with obstructive jaundice gave parallel logit-log transformation lines, suggesting immunological identity. The mean concentration of AP in normal serum (n = 104) was 1.33 +/- 0.30 (mean +/- SD) micrograms/ml. Men had significantly higher serum AP levels (1.41 +/- 0.30 micrograms/ml) (p less than 0.005) than women (1.24 +/- 0.28 micrograms/ml). Serum AP levels of patients with hepatoma (2.26 +/- 0.87 micrograms/ml) and cancer of the pancreas or the biliary tract (2.90 +/- 0.67 micrograms/ml) were significantly higher (p less than 0.005) than those of normal subjects. Patients with acute and chronic hepatitis (2.06 +/- 0.66 micrograms/ml) also had significantly higher serum AP levels (p less than 0.005) than normal subjects. In pregnant women, however, the increase in AP activity without the increase in AP concentration showed that the increased AP activity was due to an enzyme other than AP. The enzyme levels and activities in normal serum as well as in patients' sera were significantly correlated (normal, r = 0.77; patients, r = 0.95). Based on the specific activity of AP purified from human plasma, the enzyme activity splitting L-alanyl-beta-naphthylamide is due almost completely to AP in normal subjects and in patients with hepatobiliary diseases.

Adult↗
PubMed1985

Changes of plasma renin activity following intracerebroventricular administration of biologically active peptides in two-kidney, one clip hypertensive rats.

We studied the effects of intracerebroventricular (ICV) administration of angiotensin II (ANG II), bradykinin (BK), leucine-enkephalin (Leu-ENK) and neurotensin (NT) on plasma renin activity (PRA), blood pressure and heart rate in acute (less than 4 weeks) and chronic (more than 12 weeks) two-kidney, one clip (2K-1C) hypertensive rats. These four peptides all produced pressor responses. The pressor responses caused by ICV injection of ANG II, BK, Leu-ENK and NT in hypertensive rats did not differ significantly from the response in normal rats. In both acute and chronic 2K-1C hypertensive rats, ANG II and BK significantly suppressed PRA, NT did not affect PRA, and Leu-ENK produced a significant increase in PRA followed by a significant decrease in PRA. As compared to normal rats, suppression of PRA by ANG II and NT was attenuated or abolished but BK and Leu-ENK produced significant reductions in PRA in 2K-1C hypertensive rats. The results indicate that the effects of these four centrally administered peptides on blood pressure, heart rate and PRA in acute and chronic 2K-1C hypertensive rats were not essentially different from those in normal rats.

Angiotensin II↗
PubMed1984

Highly potent and specific inhibitors of human renin.

We designed aldehyde derivatives of small peptides representing the C-terminal portion of angiotensin I sequence as an inhibitor of human renin. Among compounds that we synthesized, benzyloxycarbonyl (Z)-Phe-His-Leucinal (compound V), Z-Pro-Phe-His-Leucinal (Compound IV) and Z-[3-(1'-naphthyl)Ala]-His-Leucinal (compound VII) markedly inhibited human renin (IC50, 7.5 X 10(-7), 3.2 X 10(-7) and 8.0 X 10(-8) mol/l, respectively). Compound VII was shown to be noncompetitive (Ki = 2.4 X 10(-7) mol/l). It did not inhibit either cathepsin D or pepsin. Compound V had slight or no inhibitory effect at the concentration of 10(-5) mol/l on six animal renins except for monkey and rabbit renins. Results obtained show that these aldehyde compounds are highly selective and species specific inhibitors for human and monkey renins.

Aldehydes↗
PubMed1984

Two different types of inactive renin in human plasma: molecular and kinetic properties.

We separated inactive renin in human plasma into two types, adsorbed and non-adsorbed, by chromatography on a concanavalin A-Sepharose column. About 75% of fresh plasma inactive renin was adsorbed to the column, and the rest passed through it. Non-adsorbed and adsorbed inactive renins were partially purified. Non-adsorbed inactive renin had a molecular weight of 48000 and an isoelectric point of 5.44. Adsorbed inactive renin had a molecular weight of 46000 and isoelectric points of 5.56 and 5.80. After activation with trypsin, both activated inactive renins were similar with respect to molecular weight (45000), thermostability, Km value (0.56 mumol/l) and pH profile. But pI values of both activated inactive renins differed. These results indicate that there exist in human plasma two different types of inactive renin which differ in carbohydrate composition.

Chemical Phenomena↗
PubMed1984

Purification and characterization of aminopeptidase N from human plasma.

Human plasma aminopeptidase N (EC 3.4.11.2) was homogeneously purified from outdated bank plasma. Purification procedures included ammonium sulfate fractionation, immunoaffinity chromatography, DEAE-cellulose column chromatography, hydroxyapatite column chromatography and Sephadex G-200 gel filtration. The final recovery of the enzyme was 18% and its specific activity was 71.6 mumol/min/mg protein. SDS-polyacrylamide gel disc electrophoresis and analytical ultracentrifugation showed the homogeneity of the enzyme. Equilibrium ultracentrifugation showed a molecular weight of 210,800. SDS-polyacrylamide gel disc electrophoresis indicated that the enzyme was a dimer consisting of two identical subunits. The isoelectric point of the enzyme was 3.9 at 4 degrees C. The amino acid composition of the enzyme was very similar to those of aminopeptidase N from human kidney, small intestine, and placenta which we have reported previously. Neutral sugar accounted for 11.6%. The Km, Vmax and Kcat values and hydrolytic coefficient (Kcat/Km) of the enzyme with L-alanyl-beta-naphthylamide as substrate were 8.7 X 10(-5) mol/l, 85.9 mumol/min/mg protein, 303/s and 3,483/mmol/l/s, respectively. The enzyme was activated by cobalt ions and markedly inhibited by amastatin. Plasma aminopeptidase N was immunologically indistinguishable from kidney aminopeptidase N.

Amino Acids↗
PubMed1984

Direct radioimmunoassay for human renin substrate and its measurement in plasma from essential hypertensive patients, diabetic patients and pregnant women.

We homogeneously purified human renin substrate from outdated bank plasma and raised antibody against it. The antibody did not cross-react with angiotensin I, angiotensin II or synthetic tetradecapeptide at concentrations of up to 160 nmol, nor did it cross-react with up to 0.2 ml of plasma from rat, rabbit or sheep. It did, however, completely cross-react with human des-angiotensin I renin substrate. A direct radioimmunoassay for human renin substrate was developed using the antibody, and the minimum detectable value of renin substrate found to be 70 pg of protein. Plasma renin substrate concentrations of normal subjects, essential hypertensive patients, diabetic patients and pregnant women were measured by direct and indirect assays. Hypertensive patients had similar concentrations of plasma renin substrate to normal subjects, whereas diabetic patients had significantly lower plasma renin substrate concentrations (p less than 0.01). The direct assay always gave a higher value than the indirect assay, and the ratios of the two assays (direct assay/indirect assay) were similar in normal subjects, hypertensive patients, diabetic patients and pregnant women.

Angiotensinogen↗
PubMed1984

An exaggerated natriuretic response to hypertonic saline infusion in the stage II (who stage classification) essential hypertensive patients.

We examined the natriuretic response to a hypertonic saline infusion in essential hypertensive patients who were subgrouped according to WHO stage classification. We studied 36 essential hypertensive patients and 17 normal subjects matched for age under the precise state of sodium balance (120 mEq sodium per day). The stage II essential hypertensive patients had exaggerated diuretic and natriuretic responses following the infusion of 525 ml of saline containing 120 mEq sodium for 1 hour. Our results suggest that development of essential hypertension induces a functional state that resembles expansion of extracellular fluid volume.

Adult↗
PubMed1984

Changes of plasma renin activity by intracerebroventricular administration of biological active peptides in conscious rats.

We studied the effects of intracerebroventricular administration of angiotensin II (ANG II), bradykinin (BK), leucine-enkephalin (Leu-ENK) and neurotensin (NT) on plasma renin activity (PRA), blood pressure and heart rate in conscious and unrestrained rats. Five microliters of each peptide solution was injected into the lateral cerebral ventricle. These four peptides all produced pressor effects after intracerebroventricular injection. ANG II and NT significantly suppressed PRA, BK did not affect PRA, and Leu-ENK significantly increased PRA. The central peptidergic stimulation caused by these four peptides increased blood pressures in conscious rats but showed different effects on PRA.

Angiotensin II↗
PubMed1984

A family with a high serum aminopeptidase (microsomal) activity: properties of the enzyme from serum of the propositus.

We found a family with a high activity for hydrolyzing L-alanyl-beta-naphthylamide in their serum. This enzyme was confirmed to be aminopeptidase (microsomal) (EC 3.4.11.2) by means of immunological experiments involving anti-human kidney aminopeptidase (microsomal) antibody. We could not find the cause of the increased activity from the results of clinical and laboratory examinations. The enzyme from the propositus resembled that from the serum of normal subjects in molecular mass (240 000 Da), Km value (87 mumol/L), and degree of inhibition by antiserum to human kidney aminopeptidase (microsomal). It differed from the normal enzyme with respect to electrophoretic mobility (R1 value, 0.58; normal, 0.51), isoelectric point (pI, pH 3.4; normal, pH 3.8), and heat stability (more labile than normal). From information on this family and another one reported in the Japanese literature, we suggest that the mode of inheritance of a high activity of serum aminopeptidase (microsomal) may be autosomal dominant.

Adolescent↗
PubMed1984

Orthostatic hypertension with nephroptosis and aortitis disease.

A 53-year-old woman with nephroptosis and aortitis disease was found also to have orthostatic hypertension. When standing, she had high renin levels and normal catecholamine values, with a reduced baroreflex sensitivity. This orthostatic hypertension largely may be due to an activation of the renin system caused by nephroptosis and partly due to a reduced baroreflex sensitivity caused by aortitis. Captopril and propranolol hydrochloride were effective for the treatment of hypertension.

Aortitis↗
PubMed1983

Activation and molecular weight changes of human plasma inactive renin by proteolytic enzymes.

By treating human plasma with trypsin (1 mg/ml), 3 different peaks of renin activity were detected by a gel filtration on Ultrogel AcA 44. The molecular weights of these activated renins were estimated to be 47,000, 45,000 and 43,000 daltons, respectively. 2) The molecular weight of human plasma active renin partially purified was 43,000 daltons. After treatment with neuraminidase, the molecular weight decreased to 38,000 daltons. 3) When the partially purified plasma inactive renin, which was completely separated from active renin, was activated by trypsin, chymotrypsin, plasmin, pepsin and renin, the activated renins had different molecular weights. The highest molecular weight form (47,000-48,000) was trypsin-activated or plasmin-activated renin and the lowest molecular weight form (38,000) was renin-activated renin. 4) These results suggest that cleavage of the specific site in peptide bond of plasma inactive renin by various proteolytic enzymes results in different molecular weights of activated renins. Plasma active renin free from sialic acid is very similar to kidney renin.

Chromatography, Gel↗
PubMed1983

Effect of clonidine on blood pressure in chronic one-kidney, one-clip and two-kidney, one-clip hypertensive rats.

Oral administration of clonidine lowered the high blood pressure in two-kidney, one-clip hypertensive rats in chronic stage (three to four months), but not in one-kidney, one-clip hypertensive rats. This reduction of blood pressure was well correlated with decrease in plasma renin concentration, but not with decrease in urinary noradrenaline excretion. These results suggest that the reduction of blood pressure in two-kidney, one-clip hypertensive rats may be due to reduced renin release through the action of clonidine, while in one-kidney, one-clip hypertensive rats the sympathetic nervous activity may play little or no role in the maintenance of high blood pressure.

Animals↗
PubMed1983

Different mechanisms maintaining high blood pressure in chronic one-kidney, one-clip, and two-kidney, one-clip hypertensive rats.

To evaluate the difference of the blood pressure regulating mechanisms of chronic (12-14 weeks) one-kidney, one-clip (1K-1C) and chronic two-kidney, one-clip (2K-1C) hypertensive rats, we administered captopril, captopril plus indomethacin, and indomethacin to the rats. Pretreatment values of plasma renin concentration, plasma aldosterone concentration and urinary kallikrein excretion were significantly higher in 2K-1C than in 1K-1C hypertensive rats. Captopril-induced blood pressure reduction was greater in 2K-1C than in 1K-1C hypertensive rats. When captopril was administered to the rats treated with indomethacin, captopril-induced blood pressure reduction was attenuated only in 2K-1C hypertensive rats. Indomethacin produced renal impairment and further raised the blood pressure in 1K-1C hypertensive rats, but did not in 2K-1C hypertensive rats. These results suggest that the renin-angiotensin system functions to maintain high blood pressure more predominantly in chronic 2K-1C than in 1K-1C hypertensive rats. The renal kallikrein-kinin system is suppressed in chronic 1K-1C hypertensive rats but not in 2K-1C hypertensive rats. The renal prostaglandin system is more important for regulating the renal circulation in chronic 1K-1C than in 2K-1C hypertensive rats.

Aldosterone↗