Search PubMed⌕ Search

Biomedical subjects

T Saruta

Publications and source records attributed to T Saruta.

At least 469 records · Page 26Linked to original sources
PubMed1987

Effects of atrial natriuretic peptide on renal function and renin release in the isolated perfused rat kidney.

The effects of synthetic atrial natriuretic peptide (ANP) on the renal hemodynamics, glomerular filtration rate (GFR), fluid and electrolyte excretion and renin release were studied in the isolated perfused rat kidney (IPK). When 10(-9) mol of ANP was administered in 75 ml of perfusate, the renal vascular resistance (RVR) was transiently decreased for 3 to 5 min, thereafter increased for 30 min and then tended to return to the control level. ANP increased the GFR (0.55 +/- 0.08 to 0.71 +/- 0.07 ml/min), urine flow (UV) (0.018 +/- 0.002 to 0.194 +/- 0.028 ml/min), absolute Na excretion (UNaV) (1.83 +/- 0.03 to 17.93 +/- 2.71 microEq/min) and absolute K excretion (UKV) (0.67 +/- 0.13 to 2.33 +/- 0.18 microEq/min). The addition of indomethacin or mefenamic acid to the perfusate before the administration of ANP exerted no influence on any of the effects of ANP. Renin release was inhibited by approximately 50% compared to the ANP-free control group. With the administration of ANP, UV and UNaV reached a peak 15-20 min after the GFR reached a peak and remained elevated after the GFR fell below the control level. These findings suggest that 10(-9) mol of ANP causes natriuresis and renin suppression in the IPK, and that the natriuresis is prostaglandin-independent and cannot be explained only by an increase in GFR.

Animals↗
PubMed1987

Characterization of neurohormonal changes following the production of the benign and malignant phases of two-kidney, two-clip Goldblatt hypertension.

The neurohormonal contribution to high blood pressure was investigated in 9 conscious two-kidney, two-clip Goldblatt (2K2C) hypertensive dogs during evolution of the benign and malignant phases after application of bilateral renal clips (BRC). Serial measurements were taken of the plasma renin activity (PRA), plasma angiotensin I-immunoreactivity (Ang I-ir), plasma angiotensin II-ir (Ang II-ir), renin substrate (RS) catecholamines [epinephrine (Epi) and norepinephrine (NE)] and vasopressin (AVP). Immediately after BRC, the elevation of the blood pressure (86 +/- 3 to 110 +/- 3 mmHg, p less than 0.01) was associated with an increase in heart rate (93 +/- 3 to 114 +/- 9 beats/min, p less than 0.01). These hemodynamic changes were accompanied by increases in PRA, Ang I-ir, Ang II-ir, Epi, NE and AVP. The renin angiotensin system was activated throughout the 3 week period following BRC, as indicated by increases in PRA, Ang I-ir and Ang II-ir. Catecholamines were elevated immediately after BRC, followed by a return toward the control values. AVP underwent a slight but not significant elevation after BRC, which was sustained during the 3 weeks. Production of malignant hypertension was affected by occlusion of one of the adjustable renal clips 3 weeks after BRC. A marked elevation of the blood pressure was associated with significant increases in PRA, Ang I-ir, Ang II-ir, Epi, NE and AVP, compared with the pre-occlusion values. In addition, pharmacologic experiments were performed in 6 of 9 dogs. Administration of angiotensin I converting enzyme inhibitor (SQ 14225) reduced the blood pressure both in the benign and malignant phases of 2K2C renovascular hypertension, and a ganglionic blocking agent (hexamethonium) also decreased the blood pressure. However, a specific, vascular acting AVP antagonist failed to reduce the blood pressure significantly. From this study, it seems likely that severe renal ischemia caused by renal clipping caused the activation of the renin-angiotensin and the sympathetic nervous system and elevation of serum vasopressin. However, there are no apparent differences between the benign and malignant phases of renovascular hypertension, except for the marked elevation of neurohormone levels in malignant hypertension.

Angiotensin I↗
PubMed1987

Effects of nicardipine on the systemic and renal hemodynamics in acutely elevated blood pressure induced by vasoactive agents in conscious rabbits.

The effects of the calcium antagonist, nicardipine, on blood pressure and renal hemodynamics were examined in rabbits with norepinephrine- and angiotensin II-induced elevation of blood pressure. With norepinephrine-infusion, the mean arterial pressure increased from 84 +/- 4 to 118 +/- 4 mmHg accompanied by decreases in heart rate (10%) and renal blood flow (45%). In contrast to the changes in renal blood flow with norepinephrine-infusion, renal blood flow following angiotensin II-induced elevation of blood pressure was decreased by more than 60% at the same degree of elevation of mean arterial pressure. Both intravenous and intrarenal administration of nicardipine (1 microgram/kg) reduced the mean arterial pressure and restored the decreased heart rate and renal blood flow in both norepinephrine- and angiotensin II-infused animals. Intrarenal injection of nicardipine decreased the elevated mean arterial pressure of angiotensin II-induced hypertension more than did intravenous injection (16 +/- 2 vs. 11 +/- 3 mmHg, p less than 0.05). Renal nerve denervation did not lead to any significant effects on the mean arterial pressure, heart rate and renal blood flow following intravenous or intrarenal injection of nicardipine in norepinephrine-infused animals. On the other hand, in angiotensin II-induced elevation of blood pressure, the potentiated hypotensive effect of intrarenal injection of nicardipine was lost in renally denervated animals. In conclusion, the calcium antagonist, nicardipine, was shown to reduce the acutely elevated blood pressure caused by norepinephrine or angiotensin II. In angiotensin II-induced elevation of blood pressure, the renal vasculature may play a more important role in both pressor and depressor aspects in the regulation of blood pressure as compared to its role in norepinephrine-induced hypertension.

Angiotensin II↗
PubMed1987

Effect of calcium supplementation on blood pressure in essential hypertensive subjects.

The effect of calcium supplementation on blood pressure was studied in three groups: eight normotensive subjects, 14 borderline essential hypertensive subjects, and 11 established essential hypertensive subjects (EEH). All subjects were outpatients and were given 6 g of calcium lactate (779 mg of elemental calcium) daily for 16 weeks. In EEH, systolic blood pressure was decreased significantly by 6 mmHg, but diastolic blood pressure was not decreased significantly (2 mmHg). In other groups, blood pressure was not reduced significantly. In all groups, urinary excretion of calcium was increased significantly but urinary excretion of other electrolytes, such as sodium, potassium and phosphate did not change. Serum electrolytes, various hormones, such as parathyroid hormone, 1-25(OH)2D3, 25OHD3, plasma renin activity, plasma aldosterone, plasma norepinephrine and epinephrine, and cardiac output did not change throughout this study. There were no adverse effects observed during this trial. From these results, it was concluded that daily administration of 6 g of calcium lactate produces a slight antihypertensive effect in EEH, and that this might be useful as a supplementary treatment for essential hypertension, especially in the aged.

Adult↗
PubMed1987

Antihypertensive action of angiotensin-I converting enzyme inhibitors in the kidney.

In order to elucidate the antihypertensive action of angiotensin-I converting enzyme inhibitors (CEIs) in the kidney, intrarenal (IR) administration of CEIs was performed in norepinephrine (NE) or angiotensin-II (AII) induced acute hypertension in conscious unrestrained rabbits. IR administration of the two kinds of CEIs, captopril (5 mg/kg) and MK-422 (1 mg/kg), dose which caused no significant effect when injected intravenously, elicited a prompt and marked depressor action in NE but not in AII induced hypertension. In addition, IR infusion of the angiotensin-II analogue, saralasin (2 and 10 micrograms/kg/min) showed no depressor effect in NE induced acute hypertension. These results indicate that the kidney plays an important role in the depressor action of CEIs in NE but not in AII induced hypertension and this effect may not be related to the IR renin-angiotensin system.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Short- and long-term efficacy of nifedipine in hypertensive patients with impaired renal function, with special reference to influencing factors.

Both the antihypertensive efficacy and side effects of nifedipine were investigated in hypertensive patients with impaired renal function (n = 44) in short-term (7 days) and long-term (6 months) therapeutic trials. Comparable hypotensive effects were obtained in both the short- and long-term studies (from 184 +/- 4.6/108 +/- 2.8 to 166 +/- 4.6/97 +/- 3.2 mmHg, and from 178 +/- 4.2/108 +/- 2.1 to 157 +/- 4.4/95 +/- 2.4 mmHg, respectively). In the short-term study (n = 20), the antihypertensive effect was significantly related to the pretreatment blood pressure (r = 0.51) and inversely related to the plasma renin activity (PRA) (r = -0.61; p less than 0.05). However, it was not related to age or reciprocal value of the pretreatment serum creatinine. In the long-term study (n = 24), blood-pressure-lowering effects of nifedipine were found to depend on the reciprocal value of the serum creatinine but not on PRA. The blood urea nitrogen and creatinine were not changed significantly during the observation period. Side effects occurred in 8 of the 44 patients, but severe side effects necessitating termination of administration were observed in only 2 patients. These results indicate that nifedipine is effective in both the short- and long-term treatment of hypertensives patients with impaired renal function. Impaired renal function is a key factor in the hypotensive effects of nifedipine in long-term therapy.

Adult↗
PubMed1986

[Intrapericardial pheochromocytoma: a case report and review of the literature].

A patient with intrapericardial pheochromocytoma is presented and the literature on this subject is reviewed. The patient was a 45-year-old housewife who was first referred to Keio University hospital in February 1981 for a 6-year-history of headaches, palpitations and excessive sweating. An episode of hypertensive crisis was observed during surgery for myoma uteri 3 months before her admission. On physical examination, the patient was a normal-appearing, pleasant woman. Supine blood pressure was 130/80 mmHg and standing blood pressure was 124/72 mmHg. Results of routine laboratory studies (including fasting serum glucose and calcium determinations and thyroid function tests) were normal. A 24-hour-urine collection showed VMA level of 10.5 mg and noradrenaline of 809 micrograms. Also repeated measurements of plasma noradrenaline on supine position revealed averages of 2.45 ng/ml. These high levels of catecholamines, clinical manifestations, and provocative tests including a metoclopramide test were strongly suggestive of pheochromocytoma, and further studies for determination of the localization were performed. Results of computed tomography (CT), adrenal scintigraphy using 131I-adosterol and selective venous sampling for catecholamines were equivocal. Then she was followed in an outpatient clinic and treated with alpha- and beta-blocker. In October 1985, she was readmitted to our hospital because of paroxysms which had gradually increased in frequency and severity. Extensive venous sampling in order to determine the localization of the tumor was performed after demonstration of an increased uptake area in the anterior thorax in 131I-metaiodobenzylguanidine scintigraphy. Further, an anterior mediastinal mass was identified in the CT scan of the chest with contrast material. Finally, a thoracic angiogram revealed that the tumor was highly vascular and was fed by the branch of the left internal mammary artery. In January 1986, the patient underwent middle sternotomy with cardiopulmonary bypass. A 4.5 by 3.5 by 3.0 cm soft, dark brown tumor was found on the anterior surface of the heart and excised without difficulty. The tumor seemed to arise from the root of the aorta and main pulmonary artery, and extended inferiorly over the anterior surface of the right ventricle. It was also fed by branches of the right coronary artery. Histologically, the resected tumor was compatible with pheochromocytoma. The tumor content of noradrenaline was 3.34 mg/g wet tissue; however, adrenaline and dopamine were not detected. The postoperative course was uneventful.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Iodobenzylguanidine↗
PubMed1986

Metabolism of bradykinin in isolated perfused rat kidney. Measurement of kininase activity in perfusate and urine.

The effect of bradykinin and kininase on renal function and the metabolism of bradykinin in the kidney were examined in isolated perfused rat kidney. In this experimental system, exogenous bradykinin did not affect the water and electrolyte handling by the kidney. Most of bradykinin and kininase in urine were derived from kidney but not from circulating medium. Kininase II may not have a major role in bradykinin destruction by the kidney.

Animals↗
PubMed1986

Urinary dopamine excretion in normotensive subjects with or without family history of hypertension.

To define the role of the renal dopaminergic system in the pathogenesis of essential hypertension, urinary free dopamine excretion was examined in 23 normotensive subjects who had one or more first-degree relatives with essential hypertension, and also in 36 matched control subjects without any such family history. The group urinary dopamine excretion and urinary sodium excretion were not different. However, a significant urine dopamine-sodium relationship was apparent in the controls but not in the relatives due to relatively high dopamine output in those with lower sodium excretion. The two groups were similar as regards blood pressure (BP), plasma renin activity (PRA), prolactin and catecholamines. These findings demonstrate an alteration in the urine dopamine-sodium relationship in some normotensive subjects with genetic risk of hypertension.

Adult↗
PubMed1986

Effect of a calcium entry blocker on blood pressure, plasma renin activity, aldosterone and catecholamines in normotensive subjects.

The effects of the calcium entry blocker nifedipine on blood pressure, heart rate, plasma renin activity, aldosterone, noradrenaline and adrenaline were studied in 23 normotensive subjects in the supine and upright positions. Nifedipine, 10 mg administered sublingually, lowered mean blood pressure and increased heart rate, plasma noradrenaline and renin activity without increasing plasma aldosterone in the supine position. The increase in plasma aldosterone in response to upright posture was inhibited by nifedipine, whereas the rise in plasma noradrenaline was augmented. These results suggest that intracellular calcium is important as a regulator of aldosterone secretion as well as of vascular tone in normotensive subjects.

Adolescent↗
PubMed1986

Central renin-angiotensin system and the pathogenesis of DOCA-salt hypertension in rats.

The antihypertensive effect of blockade of the brain renin-angiotensin system (brain RAS) was investigated in DOCA (deoxycorticosterone acetate)-salt hypertensive rats. Continuous intracerebroventricular (ICV) administration of SQ14225 (SQ; 1.25 micrograms X 0.5 microliter-1 X h-1) for 7 days attenuated the increase in blood pressure (99 +/- 5 vs. 116 +/- 4 mmHg on the 7th day) and also reduced the elevation of blood pressure (157 +/- 7 vs. 138 +/- 6 mmHg) in these hypertensive rats. Attenuation of increasing blood pressure in the developing phase following ICV SQ treatment was accompanied by decrease of fluid intake and prevention of elevation of the plasma vasopressin. In the established phase, in addition to reduction of the plasma vasopressin and decrease of fluid intake, restoration of the impaired baroreceptor reflexes was brought about by ICV SQ treatment. These results indicate that the brain RAS strongly influences the regulation of blood pressure in DOCA-salt hypertensive rats and that its mechanism of action is closely related to changes in sodium excretion, vasopressin, and the baroreceptor reflexes.

Aldosterone↗
PubMed1986

Synergistic action of angiotensin II on norepinephrine-induced prostaglandin release from rat glomeruli.

The effects of vasoactive substances on the release of prostaglandin (PG) and thromboxane (TX) from isolated rat glomeruli were investigated. The PGE2, PGF2 alpha, 6-keto-PGF1 alpha, and TXB2 release during 60 min into Krebs-Henseleit medium was assessed by radioimmunoassay following extraction. Norepinephrine (NE) stimulated PGE2 (from 2,117 +/- 117 to 3,968 +/- 182 pg X mg protein-1 X 60 min-1, P less than 0.01) at a concentration of 10(-4)M and PGF2 alpha (from 2,748 +/- 285 to 8,535 +/- 495 pg X mg protein-1 X 60 min-1, P less than 0.01) at a concentration of 10(-5)M. However, neither angiotensin II (ANG II) nor arginine vasopressin (AVP) affected the release of PG and TXB2 at concentrations up to 10(-5)M. In the presence of 10(-5) M NE, ANG II enhanced the release of PGE2 (from 3,307 +/- 207 to 6,865 +/- 469 pg X mg protein-1 X 60 min-1., P less than 0.01) and PGF2 alpha (from 3,652 +/- 252 to 6,612 +/- 388 pg X mg protein-1 X 60 min-1, P less than 0.01) at a concentration of 10(-8)M, whereas AVP lacked any similar effect. These results indicate that catecholamine acts as a major stimulant for the release of PG from isolated glomeruli via alpha-receptors. ANG II may work in cooperation with catecholamine, but AVP appears to play little role.

Angiotensin II↗
PubMed1986

Multiple factors contribute to the pathogenesis of hypertension in Cushing's syndrome.

The mechanisms causing high blood pressure in patients with Cushing's syndrome were investigated by measurements of humoral factors and pharmacological maneuvers. Twelve patients with adrenal adenomas were studied. The mean systolic and diastolic pressures of the patients were 171 +/- 28 and 109 +/- 15 mm Hg (+/- SEM), respectively, which were significantly higher than those of normal subjects. PRA, plasma renin concentration, plasma renin substrate, plasma cortisol, plasma aldosterone, urinary kallikrein, and urinary prostaglandin E2 were measured as the humoral factors. PC values were markedly elevated in patients with Cushing's syndrome. Among the components of the renin-angiotensin system, only plasma renin substrate was increased. Urinary kallikrein and prostaglandin E2 were decreased in patients with Cushing's syndrome. Oral administration of captopril lowered blood pressure, but infusion of an angiotensin II analog did not. Furthermore, the pressor responses to infusion of both norepinephrine and angiotensin II were increased. We conclude that blood pressure is elevated in patients with Cushing's syndrome because they have enhanced pressor responses to vasoactive substances, suppression of depressor systems, and some abnormalities of the renin-angiotensin system.

Adenoma↗
PubMed1986

Atrial natriuretic factor does not stimulate prostaglandin synthesis in isolated rat glomeruli.

The effect of alpha-human atrial natriuretic polypeptide (alpha-hANP) on the synthesis of prostaglandins was studied in isolated rat glomeruli. Glomeruli were isolated by a passive sieving technique according to the method of Misra and were incubated at 37 degrees C for 60 min in the presence (Group II: 10(-6) M, Group III: 10(-5) M) or absence (Group I: control) of alpha-hANP. Furthermore, glomeruli were incubated with arachidonic acid (10(-5), 10(-4), and 10(-3) M) and at the end of the incubation period trypan blue was added to the glomerular suspension. The presence of alpha-hANP (10(-6) and 10(-5) M) caused no significant difference in prostaglandin synthesis as compared with the control. On the other hand, arachidonic acid stimulated prostaglandin synthesis and the glomerular preparation was not stained by trypan blue, indicating that they remained viable. These results suggest that alpha-hANP does not directly affect the prostaglandin synthesis in isolated rat glomeruli.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Changes in central and peripheral renin-angiotensin system after furosemide injection.

To examine the effects of acute stimulation on the peripheral and central renin-angiotensin system, simultaneous sampling of blood and cerebrospinal fluid (CSF) for measurements of plasma renin activity (PRA), plasma angiotensin I-immunoreactivity (PAng I-ir), plasma angiotensin II-immunoreactivity (PAng II-ir), plasma angiotensinogen and cerebrospinal fluid angiotensin II-ir (CSF Ang II-ir) and CSF angiotensinogen was carried out following intravenous injection of furosemide (5 mg/kg) in conscious dogs. Administration of furosemide induced marked increases in PRA, Ang I-ir, PAng II-ir and CSF Ang II-ir, however, neither plasma nor CSF angiotensinogen was changed. Furthermore, a relatively large dose (20 mg/kg/min) of intravenously infused synthetic Ang II for 20 min produced a five-fold increase in PAng II-ir compared with no significant increase in CSF Ang II-ir. In spite of significant suppression of PRA and PAng I-ir, there were no significant changes in either plasma or CSF angiotensinogen. These results primarily suggest that the peripheral and the brain renin-angiotensin systems may be linked and that acute changes in the peripheral renin-angiotensin system do not alter either plasma or CSF angiotensinogen.

Angiotensin I↗
PubMed1986

Effects of calcium loading on blood pressure in spontaneously hypertensive rats: attenuation of the vascular reactivity.

The effects of oral calcium loading on the blood pressure of spontaneously hypertensive rats (SHR) (n = 20) and age-matched normotensive Wistar-Kyoto rats (WKY) (n = 16) were investigated. Calcium loading was performed by adding 1.5% CaCl2 (Calcium chloride) to the drinking water. Calcium loading attenuated the development of hypertension in the SHR but not in the WKY, and at the end of a 3 week experiment, systolic blood pressure was 171+2 vs 197+3 mmHg (P less than 0.01). In spite of this reduction of blood pressure, there were no significant changes in sodium-water balance, plasma levels of norepinephrine and epinephrine, plasma renin activity, plasma aldosterone concentration and serum electrolytes due to the calcium treatment. On this basis, the depressor mechanism of calcium loading in the SHR was studied by observing the pressor response to norepinephrine and the vascular reactivity to norepinephrine in hind limb perfusion. It was found that both the pressor response and the vascular reactivity were significantly attenuated by the calcium treatment in the SHR but not in the WKY. These results suggest that the antihypertensive effects of calcium treatment in SHR may depend mainly on attenuation of the vascular reactivity.

Administration, Oral↗