Biomedical subjects
Publications and source records attributed to T Saruta.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
1. To examine the possible participation of the brain iso-renin-angiotensin system in the control of blood pressure, as well as in the regulation of plasma renin activity, saralasin and captopril were injected into the cerebral ventricles of three types of experimental hypertensive rats with different plasma renin profiles. 2. Injection of saralasin and captopril into the cerebral ventricles resulted in a significant decrease in blood pressure of two-kidney, one-clip Goldblatt hypertensive rats (11 +/- 2 and 9 +/- 3 mmHg respectively) and that of spontaneously hypertensive rats (13 +/- 2 and 12 +/- 2 mmHg respectively), but in deoxycorticosterone (DOC)-salt hypertensive rats injection of these two agents showed a significant increase in blood pressure (13 +/- 2 and 12 +/- 3 mmHg respectively). 3. The plasma renin activity was markedly decreased after injection of saralasin and captopril into the cerebral ventricles of two-kidney, one-clip Goldblatt hypertensive rats. Conversely, in DOC-salt hypertensive rats, the plasma renin activity was markedly increased after injection of these two agents. In spontaneously hypertensive rats these agents caused no significant change in plasma renin activity. 4. These findings suggest that the brain iso-renin-angiotensin system participates in the central regulation of blood pressure and may be responsible for modulation of the peripheral renin-angiotensin system.
1. In conscious rats, intracerebroventricular injection of dopamine resulted in a decrease in blood pressure, whereas injection of metoclopramide, the dopamine antagonist, produced an increase in blood pressure. The central depressor effect of dopamine was attenuated by a subpressor pretreatment with intraventricular metoclopramide, but not by phentolamine. 2. Intravenous administration of dopamine increase blood pressure. This increase in blood pressure was almost completely abolished by intravenous phentolamine. Metoclopramide, when injected intravenously, did not reduce any change in blood pressure. 3. Plasma renin activity and plasma aldosterone concentration were decreased by intraventricular injection of dopamine, and increased by that of metoclopramide. In contrast, intravenous administration of metoclopramide increased plasma aldosterone concentration without changing plasma renin activity. Plasma concentrations of potassium, sodium and corticosterone were not affected by these treatments. 4. These results suggest that the dopaminergic system in the brain, but not in the systemic circulation, is involved in the regulation of blood pressure. It is also suggested that the central dopaminergic system participates in the regulation of aldosterone secretion by changes in the renin--angiotensin axis, whereas the peripheral dopaminergic modulation of aldosterone secretion appears to occur independently of the renin--angiotensin system.
To investigate the relation between renin content in each juxtaglomerular apparatus and reduction of plasma renin activity (PRA) with aging, the PRA and microdissected superficial or juxtamedullary single nephron renin content (SNRC) were determined in 5 young (3-6 months) and 5 aged (13-18 months) rats fed on a normal salt diet. The mean value of the PRA in the aged group was significantly lower than that of the young group. A highly significant correlation was found between the RPA and mean values of the superficial SNRC. The mean values of both the superficial and deep SNRC in the aged rats were significantly lower than those of the corresponding zones in the young rats. It is suggested that decreased synthesis of renin in each juxtaglomerular apparatus is an important factor in the decreased PRA observed with aging.
The role of the renin-angiotensin system in the control of aldosterone and other mineralocorticoids was studied in 9 hyperkalemic patients with chronic renal failure showing mild azotemia (group I) and 6 normokalemic patients with chronic renal failure showing creatinine clearance similar to that in group I (group II). In group I, the plasma renin activity (PRA) was significantly low and plasma aldosterone (PAC) and 18-hydroxycortisterone (18-OH-B) were also significantly reduced. In group II, PRA was normal or slightly increased, and PAC and 18-OH-B were also normal or slightly increased. Both the PAC and 18-OH-B in group I were stimulated by ACTH and angiotensin II, although the responses were less than those in group II. In 2 patients of group I where PRA moved into the normal range after administration of furosemide, the plasma 18-OH-B and PAC also reached the lower limit of normal. These results suggest that suppression of the renin-angiotensin system is probably related to functional disturbance in the conversion from B to 18-OH-B and/or 18-OH-B to aldosterone in most abnormally hyperkalemic patients with chronic renal failure.
Renin production and release induced by angiotensin I converting enzyme inhibitor (CEI), SQ 14225, were studied in male Wistar rats. Acute studies on the effects of CEI (4.6 mumol/kg, i.m. every 6 h for 48 H) in rats revealed a significant reduction in angiotensin II levels and a marked increase in plasma renin activity (PRA). There were no appreciable changes in renal content (RRC) and the juxtaglomerular cell granulation index (JGI). In rats which had received CEI in their drinking water (0.92 mumol/ml) for 12 days, angiotensin II levels were decreased markedly and urinary excretion of sodium was increased, but the reduction in blood pressure was slight. PRA, JGI and RRC were markedly increased in these animals. The kidneys of CEI-treated rats exhibited conspicuous vascular dilatation. CEI treatment of sodium-depleted rats resulted in a reduction of the increased JGI and RRC and in a further increase in PRA. Our findings suggest that CEI administration may initially effect stimulation of renin release from the juxtaglomerular apparatus and that prolonged CEI administration results in a gradual stimulation of renin production.
The role of the renin-angiotensin system in the development of hypertension was studied by infusing an angiotensin II analog, 1-Sar, 8-Ile angiotensin II, in women with toxemia and women on estrogen-containing oral contraceptives or estrogen treatment. In 3 of 4 women who developed hypertension on oral contraceptives or estrogen treatment, the blood pressure was reduced with the infusion of 1-Sar, 8-Ile angiotensin II. In 3 women who remained normotensive on oral contraceptives or estrogen treatment, the blood pressure was not reduced, although there was no significant difference in plasma renin activity (PRA) between the women who developed hypertension and those who remained normotensive on oral contraceptives. In 6 pregnant women who developed hypertension, the blood pressure increased remarkably with the infusion of 1-Sar, 8-Ile angiotensin II, although PRA was increased significantly in all of them. In these women, however, sodium excretion was less than that in normal pregnant women. In 4 normal pregnant women, the blood pressure remained unchanged or increased slightly, and PRA was almost similar to that of women who developed hypertension. The above results suggest that increased PRA in women who developed hypertension whilst on estrogen-containing oral contraceptives or estrogen treatment is more closely related to the development or maintenance of hypertension than that in pregnant women who develop hypertension, although there remains a possibility that the response of blood pressure to 1-Sar, 8-Ile angiotensin II in pregnant women who develop hypertension is influenced by sodium retention.
To investigate the role of the central and peripheral dopaminergic systems in the control of the renin-angiotensin-aldosterone system in conscious rats, dopamine or its antagonist, metoclopramide, was injected intravenously (i.v.) and intracerebroventricularly (i.c.v.). Dopamine (100 micrograms/kg), when injected i.c.v., decreased plasma renin activity (PRA) and plasma aldosterone concentration (PA), while metoclopramide (50 micrograms/kg, i.c.v.) increased both of them. Intravenous administration of dopamine (1 microgram/kg/min) did not produce significant changes in either PRA or PA. In contrast, metoclopramide (500 micrograms/kg, i.v.) increased PA, which was not accompanied by any change in PRA. Blood pressure was decreased by i.c.v. administration of dopamine and increased by i.c.v. injection of metoclopramide, whereas no change in blood pressure was observed when these compounds were administered i.v. Dopamine and metoclopramide, injected i.v. or i.c.v., did not produce significant changes in plasma sodium, potassium and corticosterone concentrations. These results suggest that the dopaminergic system in the brain regulates renin secretion, thereby changing PA. In contrast, dopamine receptors of the adrenal glands may inhibit aldosterone secretion, which is not mediated by changes in the renin-angiotensin system, plasma potassium and ACTH.
The present study was performed to assess the influence of potassium on blood pressure in deoxycorticosterone (DOCA) salt hypertensive rats. The effects of potassium administration on the systolic blood pressure, fluid intake, urine volume, excretion of sodium and potassium, serum sodium and potassium, plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were investigated both during the first 2 weeks of development of DOCA salt hypertension and during the next 2 weeks of established DOCA salt hypertension. Potassium administration prevented the development of DOCA salt hypertension and reduced the blood pressure in established DOCA salt hypertension. Fluid intake, urine volume, and excretion of sodium and potassium appeared to be markedly increased in rats treated with potassium. The levels of serum sodium and potassium were unchanged by potassium loading. Both the PRA and PAC which were suppressed in DOCA salt hypertensive rats, were reversed in rats treated by potassium loading. It is suggested that the elevation of blood pressure may be prevented and the increased blood pressure reduced mainly by the diuresis and natriuresis caused by potassium loading.
In the perfused rat mesenteric vascular bed, the effects of captopril and prostaglandin I2 (PGI2) on the vasoconstrictor responses to norepinephrine or potassium chloride were studied. Captopril or PGI2 in the perfusate attenuated the vascular responses to norepinephrine in a dose-related manner, while these substances had no effect on the vascular contractions induced by potassium chloride. In preparations treated with indomethacin, the inhibitory effect of captopril on the vascular response to norepinephrine was similar to that found in the untreated preparations. These results suggest that, although the effects of captopril on the vascular reactivity is similar to that of PGI2, the direct vascular action of captopril is not mediated by the synthesis of prostaglandins in the vascular bed.
The effects of dexamethasone (DEX) on systolic blood pressure, sodium balance and the renin-angiotensin system were studied in rats. DEX significantly increased systolic blood pressure within three days of its administration, but this effect of DEX on blood pressure was not enhanced by concurrent use of saline solution. In DEX-treated rats, urine volume was significantly increased and urinary sodium excretion showed a tendency toward a slight increase compared to control rats. On the 8th day of DEX administration, plasma renin substrate (PRS) was significantly elevated compared to control rats, whereas plasma aldosterone concentration (PAC) was not significantly different from that of control rats. These results suggest that hypertension induced by DEX may not be dependent on sodium retention or activation of the renin-angiotensin system.
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The formation of spironolactone (S) bodies, eosinophilic laminated cytoplasmic inclusions, is induced in the aldosterone-producing cells of the human adrenal cortex after the administration of spironolactone. The aim of this study was to define the enzyme histochemical characteristics of S bodies, S-body-containing cells, and the apparently hyperplastic zona glomerulosa (zG) of adrenal tissues attached to aldosteronomas. S bodies were found in 14 of 19 aldosteronomas, in 10 of 19 adrenal tissues attached to aldosteronomas, and in the adrenal tissues in a patient with aldosteronism due to bilateral diffuse zG hyperplasia. The S bodies themselves exhibited most intense 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) activity but did not exhibit glucose-6-phosphate dehydrogenase (G6PD), NADP-dependent isocitrate dehydrogenase (NADP-ICDH), or succinate dehydrogenase (SDH) activity, confirming histochemically the origin of S bodies in the smooth endoplasmic reticulum. In two adenomas, S bodies were found to be surrounded by reaction products of acid hydrolase but were not found in the other adenomas and the remaining adrenal tissues. S-body-containing cells, irrespective of being neoplastic or not, showed enhanced 3 beta HSD, G6PD, and NADP-ICDH activity and weak SDH activity (Type I pattern of enzyme activity). Though zG was hyperplastic in most of the adrenal tissues attached to the adenomas, zG cells that did not contain S bodies showed the opposite pattern (Type II pattern) of enzyme activity (ie, weak 3 beta HSD, G6PD, and NADP-ICDH activity and intense SDH activity), in contrast to those in the adrenal tissues in a patient with aldosteronism due to bilateral diffuse zG hyperplasia (which showed the Type I pattern). The results are consistent with the view that hyperplastic zG cells, except S-body-containing cells, in the case of aldosteronoma are not hyperfunctioning. The latter cells may have enhanced but possibly abortive steroidogenic activity.