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Biomedical subjects

J Higaki

Publications and source records attributed to J Higaki.

At least 253 records · Page 14Linked to original sources
PubMed1984

A new sensitive direct radioimmunoassay for human plasma renin and its clinical application.

We developed new sensitive direct radioimmunoassay for human plasma renin. Renin was purified from Haas' preparation utilizing a pepstatin-C6-Sepharose affinity chromatography. Antiserum, prepared by immunizing rabbits with the purified renin, was used for the direct radioimmunoassay at a final dilution of 1:30,000. The antibody was specific for human renal and plasma renin, but did not cross-react with cathepsin D, trypsin, or renins of mouse, dog, and rat. Radioimmunoassay was performed by the double antibody technique using the delayed tracer addition method. In this method, a standard curve was obtained over a range from 0.2 to 8.0 ng/ml. The values from our assay correlated well with total renin activity measured as the generation rate of angiotensin I after trypsin activation (r = 0.78, p less than 0.01), but correlated weakly with active renin activity. This finding disclosed that both active and inactive renin were detected by this method. In normal participants, plasma renin concentration determined by direct radioimmunoassay was increased by standing and furosemide injection. The plasma renin concentration determined by direct radioimmunoassay of patients with essential hypertension (0.7 to 1.7 ng/ml) was not significantly different from values in normal controls (0.8 to 1.9 ng/ml). The values were higher in patients with renovascular hypertension (1.6 to 2.7 ng/ml), malignant hypertension (2.8 to 3.4 ng/ml) and Bartter's syndrome (1.8 to 2.5 ng/ml), but lower in patients with primary aldosteronism (0.4 to 0.8 ng/ml) than in normal controls. This newly developed radioimmunoassay for human renin was sensitive enough to estimate the levels of renin in plasma of patients with low renin hypertension. It provides a new tool for the understanding of the renin-angiotensin system under various clinical conditions.

Adult↗
PubMed1984

Sensitive direct radio-immunoassay for human renin.

A sensitive direct human renin radio-immunoassay has been developed for clinical use. The antigen source was human renal renin purified from Haas' preparation by pepstatin-C6-sepharose affinity chromatography, this was used to prepare a specific human renin antibody. The radio-immunoassay was performed by the double antibody technique using the delayed tracer addition method. Standard curves were obtained over the range 0.2-8.0 ng/ml. Dilution curves of human renal renin and human plasma were superimposable on the standard curve. Both active and inactive renin were detected by this method, and measurements correlated well with total renin activity after trypsin activation. Intra- and inter-assay coefficients of variance were 4.6% and 5.1%, respectively. Renin concentration was higher in patients with renovascular hypertension (1.97 +/- 0.38 ng/ml, mean +/- s.d., n = 10, P less than 0.01), but lower in primary aldosteronism (0.66 +/- 0.16 ng/ml, n = 13, P less than 0.01) compared with essential hypertension (1.38 +/- 0.34 ng/ml, n = 12). This method provides a new tool for the investigation of the renin-angiotensin system in man.

Humans↗
PubMed1983

Effect of captopril on renal vascular resistance, renin, prostaglandins and kinin in the isolated perfused kidney.

Vasodilatory and natriuretic effects of captopril were studied in the isolated hog kidney perfused with modified Krebs-Ringer solution. Renal arterial infusion of captopril caused increases in releases of renin, prostaglandins (PGE2, 6-keto-PGF1 alpha and PGF2 alpha) and kinin, and was accompanied by a decrease in the renal vascular resistance and an increase in urinary sodium excretion. Indomethacin administered with captopril diminished the saluretic effect of captopril and evoked an increase in kinin, but was associated with a marked decrease in prostaglandin and renin releases, while renal vascular resistance remained decreased. Indomethacin alone did not alter vascular resistance and kinin; however, renin and prostaglandin releases were decreased. Aprotinin administered with captopril showed a decrease in releases of prostaglandins, renin and kinin without any change in vascular resistance. These results suggest that increased release of kinin induced by captopril contributes to a reduction in renal vascular resistance. Increased prostaglandin release after captopril administration may be caused by an increase in kinin without direct involvement of captopril in prostaglandin synthesis. Renal prostaglandins may enhance sodium excretion and mediate renin secretion in captopril perfusion.

Animals↗
PubMed1983

A novel purification method of human renin.

Human renal renin was isolated from a partially purified preparation, Haas' preparation step 5 material, with a remarkably high yield of 28% by a newly developed method. This method consisted of only four steps including affinity chromatography on pepstatin-aminohexyl-agarose, chromatofocusing, gel filtration and DEAE-chromatography after the initial extraction and concentration. This method enabled us to obtain pure human renin without another affinity column used by other investigators. Pure human renin had a molecular weight of 40,000 daltons as estimated by gel filtration and sodiumdodecylsulfate-polyacrylamide gel electrophoresis. The pI of purified renin was 5.6.

Chromatography, Affinity↗
PubMed1983

Plasma inactive renin in patients with hyperthyroidism.

Active and inactive PRA were measured after 1 h at rest in 16 normal controls and 20 patients with hyperthyroidism. In some of the patients these measurements were repeated after they had become euthyroid or received 90 mg propranolol for 1 week. Inactive PRA was determined as the difference between total PRA after trypsin activation and active PRA. Active PRA was significantly higher (P less than 0.01) in untreated patients than in normal subjects; however, the inactive PRA of patients was not different compared with that of normal subjects. Active PRA was normalized, and inactive PRA did not change after achievement of euthyroidism. The proportion of active of total PRA was significantly correlated with the levels of serum thyroid hormones (T3 and T4) in hyperthyroid patients (r = 0.46; P less than 0.05 and r = 0.55; P less than 0.01, respectively). The administration of propranolol reduced active PRA (P less than 0.05) and increased inactive PRA slightly but not significantly. These results indicate that in hyperthyroidism, the in vivo conversion of inactive renin to active renin is probably facilitated by increased sympathetic activity.

Adult↗
PubMed1983

Plasma inactive renin in diabetic patients with neuropathy: a role for the sympathetic nervous system in the conversion in vivo of inactive renin.

Plasma levels of active and trypsin-activatable inactive renin and catecholamines were measured in 6 diabetic patients with neuropathy (group 1), 8 diabetic patients without neuropathy (group 2) and 8 age-matched normal subjects. The effect of insulin administration on plasma active and inactive renin and plasma catecholamine levels in diabetic patients was also investigated. The levels of inactive renin were calculated as the difference between the levels of total renin after trypsin activation and those of active renin. The levels of plasma catecholamines were determined by the trihydroxyindole method. The levels of active renin were significantly lower and inactive renin was increased slightly in group 1 when compared with controls. Group 1 showed a significant reduction in plasma norepinephrine levels. Group 2 showed slightly reduced active renin, normal inactive renin and normal norepinephrine values. There was no significant difference in the levels of epinephrine between the 3 groups. After insulin injection, active renin levels were increased in groups 1 and 2. The mean increment in active renin levels was less in group 1 than in group 2. Inactive renin levels were slightly decreased in both groups. Significant increases in epinephrine and norepinephrine levels were observed following insulin administration. The mean increment in norepinephrine levels was less in group 1 than in group 2. There was a positive correlation between the mean increment in active renin and in norepinephrine levels in diabetic patients. These results suggest that the impaired conversion of inactive renin into an active form is responsible in part for the low levels of active renin in diabetics with neuropathy.

Diabetes Mellitus↗
PubMed1982

Effect of prostacyclin infusion on active and inactive renin release in the isolated perfused kidney.

The effect of prostacyclin infusion into the renal artery of the isolated perfused hog kidney on the release of active and inactive renin was investigated. Infusion of prostacyclin at a rate of 0.1 microgram/min resulted in a significant increase (p less than 0.01) in active renin and a significant fall (p less than 0.01) in inactive renin. Prostacyclin also increased urinary kallikrein excretion (p less than 0.05). The results indicate that the kidney secretes not only active renin but also inactive renin, and suggest that prostacyclin stimulates the conversion of inactive renin to the active form through the activation of the renal kallikrein system.

Animals↗
PubMed1982

Responses of active and inactive plasma renin and changes in urinary kallikrein and plasma prekallikrein to various conditions in normal subjects.

Little is known about changes in inactive plasma renin in various conditions or the in vivo activation mechanism of inactive renin. The effects of various factors known to stimulate or suppress renin release on active and inactive PRA were examined in normal subjects. Inactive PRA was determined as the difference between the total PRA after trypsin activation and active PRA. Concurrent measurements of urinary kallikrein excretion and plasma prekallikrein activity were performed to assess the possible role of renal or plasma kallikrein in in vivo activation of inactive renin. Short term stimulation with iv furosemide and ambulation, infusion of isoproterenol, and administration of captopril increased active PRA, but had little or no effect on inactive PRA. Sodium restriction and sodium loading, each for 4 days, induced parallel changes in active and inactive PRA. The administration of propranolol for 4 days decreased active PRA but did not change inactive PRA. There were no significant correlations between the changes in urinary kallikrein excretion and those in active PRA or in the proportion of active to total PRA after any short term treatments, except furosemide administration. Plasma prekallikrein activity was correlated with the proportion of active renin only during the long term sodium balance study. The present data suggest that the mechanisms ofr the control of inactive and active renin are different. Neither renal nor plasma kallikrein seems to be consistently involved in the in vivo activation of inactive renin.

Adult↗
PubMed1981

Effect of age on active and inactive plasma renin in normal subjects and in patients with essential hypertension.

The effect of age on the levels of active and trypsin-activatable inactive plasma renin was examined in 41 normal subjects and 54 patients with essential hypertension, during recumbency and after stimulation with furosemide and ambulation. Active renin levels in supine subjects and patients decreased with age. Inactive renin levels did not change with age in normal subjects, whereas in hypertensive patients they decreased with age. Following stimulation with furosemide and ambulation, the levels of active renin increased but the responsiveness to stimulus decreased with age in both groups. In contrast, inactive renin levels slightly increased after furosemide administration and ambulation, resulting in increased proportion of active to total renin. These data show that an acute stimulation with furosemide and ambulation affects mainly the active form of plasma renin, and the effect of age on inactive plasma renin in normal subjects may be different from that in patients with essential hypertension.

Adult↗
PubMed1980

Is normoreninemic essential hypertension caused by disordered central dopaminergic regulation?

Some investigators have reported that plasma prolactin levels are elevated in hypertensive men and that both their hyperprolactinemia and hypertension were controlled by bromocriptine, a dopamine agonist. They concluded that reduced central dopaminergic activity may be a factor in maintaining essential hypertension. We examined the serum prolactin and thyrotropin (TSH) responses to thyrotropin releasing hormone (TRH), metoclopramide (a dopamine antagonist) and bromocriptine in 10 normal and 10 hypertensive normoreninemic men. TRH caused significant increase of both prolactin and TSH and metoclopramide caused significant increase of prolactin in both normals and hypertensives. Bromocriptine suppressed prolactin and TSH significantly in both groups. There were no significant differences in prolactin and TSH levels between the normal and hypertensive groups before or during the tests. These results provide no support for the hypothesis that alterations in the activity of central dopaminergic neurons are involved in the maintenance of the elevated blood pressure of normoreninemic men with essential hypertension.

Bromocriptine↗
PubMedDate not supplied

Effect of aging on the renin angiotensin system in patients with renovascular hypertension.

The effect of aging on the renin angiotensin system (RAS) was studied in 30 patients with renovascular hypertension and 33 patients with essential hypertension. Plasma renin decreased with age in patients with renovascular hypertension and essential hypertension. However, in patients with renovascular hypertension, the change was not statistically significant. Plasma aldosterone concentration showed a tendency to decrease with age in both groups. Stimulated plasma renin activity and the net increase in plasma renin activity after captopril administration in patients with essential hypertension showed a significant decrease with age. In patients with renovascular hypertension, exaggerated response of renin secretion was observed in younger patients, but middle-aged and elderly patients did not demonstrate this hyper-responsiveness. The degree of decrease in blood pressure by administration of an angiotensin (Ang) II analog ([Sar1,Ile8] Ang II) was the same in both younger and elderly patients with either disease. These results suggest that the effect of aging on the RAS occurs not only in patients with essential hypertension, but also in patients with renovascular hypertension. Furthermore, although the Ang II analog infusion test and captopril stimulation test are considered to be useful screening tests for renovascular hypertension, we consider that the combination of Ang II analog test and captopril test may be favorable to screen renovascular hypertension, since the captopril stimulation test had a lower sensitivity in younger (under 35 years old) patients.

Adult↗