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Biomedical subjects

T Saruta

Publications and source records attributed to T Saruta.

At least 451 records · Page 25Linked to original sources
PubMed1988

Hormonal and renal responses to oral once-daily calcium entry blocker in normotensive and hypertensive persons.

A newly produced calcium entry blocker, KW3049 (Kyowa Hakko, Tokyo, Japan), which maintains its antihypertensive action for greater than 24 h, was administered orally once daily to 12 subjects (5 normotensive, 7 hypertensive) for 12 days. To elucidate its hypotensive efficacy and mechanisms of action, daily changes in blood pressure and heart rate, serial alterations in the renin-angiotensin system and sympathetic nervous system, and the renal hemodynamics were investigated. KW3049 caused a significant decrease in mean arterial pressure from 124 + 3 to 107 + 2 mm Hg, accompanied by a moderate increase in heart rate (+15%). The urine volume and urinary excretion of sodium were persistently increased in hypertensive subjects with improvement of the renal blood flow. The plasma renin activity and plasma and urinary norepinephrine (NE) increased significantly (p less than 0.05) on the sixth day and returned to baseline levels on the twelfth day. In addition to these renal and hormonal changes, the pressor responses to infused NE and angiotensin II were attenuated on the twelfth day after KW3049 administration. The above findings suggest that only once-daily administration of KW3049 is able to reduce the blood pressure without fluctuation, and its antihypertensive mechanisms are related to a natriuretic action and attenuation of pressor responses as well as to strong vasodilation.

Adult↗
PubMed1988

Hormonal responses to synthetic atrial natriuretic peptide in patients on regular hemodialysis.

The effects of atrial natriuretic peptide (ANP) on mean arterial blood pressure, heart rate, plasma renin activity, aldosterone, cortisol, norepinephrine, epinephrine and arginine vasopressin were studied in 6 anuric subjects receiving regular hemodialysis. An iv bolus injection of 8 nmol of ANP followed by infusion at 32 pmol.kg-1.min-1 for 1 h in the pre- and posthemodialysis period was performed. Basal plasma ANP was higher before than after hemodialysis. ANP administration produced a reduction in mean arterial blood pressure accompanied by an elevation of norepinephrine and of plasma renin activity (from 2.49 +/- 0.52 to 3.39 +/- 0.85 nmol.1-1.h-1 predialysis and from 2.78 +/- 0.71 to 3.15 +/- 0.86 nmol.l-1.h-1 postdialysis, respectively, mean +/- SEM; P less than 0.05). Plasma aldosterone and cortisol were significantly decreased. Plasma epinephrine and AVP remained unchanged. These hemodynamic and hormonal changes were similar in the pre- and the postdialysis period. These results suggest that 1) ANP causes a fall in mean arterial blood pressure, which in turn induces reflex tachycardia and activation of the sympathetic nervous system without diuresis; 2) the activated sympathetic nervous system as reflected in elevation of plasma norepinephrine may increase plasma renin activity; 3) reduced plasma aldosterone is not influenced by enhancement of the renin-angiotensin system; therefore, 4) reduction of plasma aldosterone as well as cortisol is probably due to direct action of ANP, and finally 5) AVP had no direct relation with ANP administration.

Adult↗
PubMed1988

Therapeutic benefits and safety of carvedilol in the treatment of renal hypertension. An open, short term study. Carvedilol Renal Hypertension Study Group in Japan.

Carvedilol, a new beta-blocker with vasodilating activity, was given orally to 9 hypertensive inpatients with impaired renal function in a dosage regimen of 5 to 20mg once daily to evaluate its clinical efficacy and safety. Treatment with carvedilol produced a significant decrease in blood pressure from 172/101 to 150/87mm Hg (p less than 0.01), but it did not cause orthostatic hypotension. Heart rate was decreased from 74.3 to 72.8 beats/min, but the decrease was not statistically significant. Serum creatinine and BUN levels were unchanged and other laboratory parameters were within normal limits. There were no side effects in any of the patients during the trial. These results suggest that carvedilol is a useful and safe drug for the treatment of renal hypertension.

Adrenergic beta-Antagonists↗
PubMed1987

Effect of ramipril, a new angiotensin converting enzyme inhibitor, on diurnal variations of blood pressure in essential hypertension.

The effect of ramipril on diurnal variations of blood pressure was studied in patients with mild to moderate essential hypertension in groups given once- (n = 18) and twice-daily (n = 21) administration with daily dosages ranging from 2.5 to 10 mg. After ramipril treatment, the blood pressure of patients in both groups was significantly reduced, and no significant differences in diurnal variation of blood pressure were observed between the 2 groups. The pulse rate did not change after administration of ramipril and no serious side effects were observed. In consideration of patient compliance, once-daily administration of ramipril seems to be optimal for the treatment of essential hypertension.

Adult↗
PubMed1987

Efficacy and safety of ramipril (HOE 498) in the treatment of hypertension: dose finding study.

An open-label, prospective multicenter trial of ramipril was performed. The agent was administered once daily at an initial dosage of 1.25 mg and this was increased, when necessary, up to 10 mg with intervals of 2 weeks for 8 weeks. Effectiveness in 46 patients with mild to moderate essential hypertension was 28.1% at a dosage of 1.25 mg, 52.2% at 2.5 mg, 69.6% at 5 mg and 78.3% at 10 mg of ramipril alone. In 27 patients receiving baseline therapy with a thiazide diuretic, a subsequent administration of ramipril showed effectiveness in 11.1% for 1.25 mg, 48.1% for 2.5 mg and 70.4% for 5 mg. Adverse effects occurred in 11.7% of patients overall and were not serious. One patient was withdrawn because of severe headache; the other patients tolerated the treatment well. A dosage of 2.5 to 10 mg of ramipril will probably be appropriate for further evaluation of the effectiveness of this agent in a double-blind study.

Adult↗
PubMed1987

The renal antihypertensive effect of angiotensin I converting enzyme inhibitors.

Intrarenal administration of angiotensin I converting enzyme (ACE) inhibitors carried out in norepinephrine- (NE; 2-4 micrograms/kg per min) or in angiotensin II- (ANG II; 60-90 ng/kg per min) induced acute hypertension in conscious unrestrained rabbits. Intrarenal administration of captopril (5 mg/kg) and MK-422 (1 mg/kg) caused no significant effect when injected intravenously. However, it showed a prompt and marked depressor effect in NE- but not in ANG II-induced hypertension. This effect was not observed after intrarenal infusion of saralasin (2 and 10 micrograms/kg per min) in NE-induced hypertension. While pretreatment with aprotinin or indomethacin failed to inhibit the depressor action, 2-bromoethylamine hydrobromide (BEA), which is known to induce necrosis of the renal papilla, produced complete abolition of the depressor effect of an intrarenal injection of MK-422 in NE-induced hypertension. These results indicate that the kidney plays an important role in the depressor action of ACE inhibitors in NE- but not in ANG II-induced acute hypertension, and that this effect may be related to the potentiation of antihypertensive renomedullary lipids rather than the inhibition of the renin-angiotensin system or the potentiation of bradykinin or prostaglandins.

Acute Disease↗
PubMed1987

Oral calcium treatment lowers blood pressure in renovascular hypertensive rats by suppressing the renin-angiotensin system.

The effects of calcium supplementation on blood pressure and its mechanisms were investigated in two-kidney, one clip renovascular hypertensive rats. Two series of experiments were performed: one was begun just after renal artery constriction, the other after the onset of hypertension. Calcium supplementation significantly attenuated the development of hypertension (systolic blood pressure: 183 +/- 8 vs 130 +/- 2 mm Hg) and was found to abate existing renovascular hypertension (systolic blood pressure: from 183 +/- 8 to 151 +/- 4 mm Hg). Calcium treatment did not cause significant alterations in fluid intake, urine volume, or urinary sodium excretion in either study. However, increased plasma renin activity and plasma aldosterone concentration were suppressed to the basal levels at the end of 3 weeks of calcium treatment (14 +/- 3 vs 8 +/- 2 ng angiotensin I/ml/hr; 530 +/- 50 vs 380 +/- 40 pg/ml). Blood pressure of calcium-treated renovascular hypertensive rats responded poorly to blockade of the renin-angiotensin system with captopril injection and angiotensin II analogue (saralasin) infusion. Further, in rats with chronic established renovascular hypertension, calcium treatment attenuated the enhanced pressor response to norepinephrine, but not to angiotensin II. These results suggest that the blood pressure-lowering actions of calcium supplementation are related primarily to suppression of renin secretion and secondarily to alteration of pressor response to norepinephrine in two-kidney, one clip renovascular hypertensive rats.

Administration, Oral↗
PubMed1987

Blood pressure response to a calcium entry blocker in normotensive subjects with or without a family history of hypertension.

The possibility that a familial background of hypertension might influence the blood pressure response to a calcium entry blocker was evaluated in 15 normotensive relatives of patients with essential hypertension and 18 normotensive subjects with no family history of hypertension. Under control conditions, blood pressure, heart rate, plasma noradrenaline, adrenaline, and renin activity did not differ between the two groups. Nifedipine, at a dose of 10 mg administered sublingually, lowered the blood pressure and increased the heart rate, plasma noradrenaline, and renin activity. The normotensive relatives of patients with essential hypertension did not differ in their responses from the normotensive subjects with no family history of hypertension, with the exception of plasma noradrenaline thirty minutes after nifedipine. These results provide evidence to suggest that there is no functional abnormality with increased dependency of vascular smooth muscle tone on calcium influx in the prehypertensive state.

Adult↗
PubMed1987

Effects of calcium loading in DOCA-salt hypertensive rats.

The effects of oral calcium loading on blood pressure (BP) of DOCA (deoxycorticosterone acetate)-salt hypertensive rats (D-S rats) were investigated. Calcium loading was performed by adding 1% CaCl2 (calcium chloride) to the drinking water. Calcium loading attenuated the development of high BP in D-S rats, and at the end of a two week experiment, BP was 141 +/- 3 (calcium treated) vs. 174 +/- 7 mmHg (non-calcium treated) (p less than 0.01). However, calcium loading did not cause any changes in BP in normotensive rats. Further, in established D-S rats [after four weeks of DOCA and 1% NaCl (sodium chloride) treatment], calcium loading for 4 weeks also reduced BP [144 +/- 6 (calcium treated) vs. 181 +/- 4 mmHg (non-calcium treated), p less than 0.01, at the end of experiment]. With calcium treatment, there were no significant changes in sodium-water balance, plasma levels of epinephrine and norepinephrine, plasma renin activity, plasma aldosterone concentration and serum electrolytes both in developing and established D-S rats. The depressor mechanism of calcium loading was studied by observing vascular responsiveness to norepinephrine both in whole body and in hind limb preparations. Vascular reactivity in both developing and established D-S rats was significantly attenuated by calcium treatment. These results suggest that the antihypertensive effects of calcium treatment in D-S rats are mainly caused by attenuation of vascular reactivity.

Aldosterone↗
PubMed1987

Hypertension in patients on chronic hemodialysis: the role of the renin-angiotensin system.

The effects of volume-loading and removal on mean blood pressure were evaluated in patients with high blood pressure and on chronic hemodialysis. Simultaneous measurements of plasma renin activity, plasma angiotensin II and plasma norepinephrine were made. The patients were divided into two groups according to their levels of plasma renin activity. Group 1 (n = 10) had a basal plasma renin activity below 2.5 ng/ml/hr while the level in group 2 (n = 5) exceeded 2.5 ng/ml/hr. The mean blood pressure of the two groups was 105 +/- 5 mmHg and 107 +/- 4 mmHg, respectively. On the day of hemodialysis, saline loading (0.5 ml/kg/min for 20 min) was followed by routine hemodialysis. The mean blood pressure rose to 113 +/- 6 mmHg in group 1. However, the patients in group 2 did not respond to volume loading and hemodialysis. The plasma renin activity, plasma angiotensin II and plasma norepinephrine were not changed by volume loading in both group 1 and 2. Volume removal by hemodialysis caused a reduction in mean blood pressure in group 2 without alteration of vasoactive hormones. In group 1, the mean blood pressure was not reduced by hemodialysis, accompanied by increases in plasma renin activity, plasma angiotensin II, and plasma norepinephrine. In the high renin group, elevated circulating angiotensin II maintained a high blood pressure and in the low renin group, the renin-angiotensin system influenced the prevention of fall in blood pressure after hemodialysis. These results suggest that the renin-angiotensin system plays an important role in the regulation of blood pressure in relation to volume status regardless of whether the plasma renin activity is high or low.

Adult↗
PubMed1987

Effect of vasoactive substances on natriuresis induced by atrial natriuretic peptide in isolated perfused rat kidneys.

We studied the interaction between synthetic atrial natriuretic peptide (ANP) and various vasoactive substances, which included isoproterenol (ISO), aminophylline (AMI), and dibutyryl cyclic AMP (dBcAMP) as vasodilators, and angiotensin II (AII) and norepinephrine (NE) as vasoconstrictors, and prazosin as an alpha-blocker in isolated perfused rat kidneys (IPK). When 10(-9) mol of ANP was administered in 75 ml of a perfusate, the renal vascular resistance (RVR) was transiently decreased for 5 min, and increased thereafter. Simultaneously, ANP increased the glomerular filtration rate (GFR), urine flow (UV), absolute Na excretion (UNaV) and absolute K excretion (UKV). All of the above mentioned effects of ANP were significantly inhibited by administering ISO, AMI or dBcAMP. On the other hand, the administration of AII and NE significantly enhanced the increases in UV and UNaV and the fractional excretion of Na induced by ANP, although AII and NE had no influence on the changes in RVR and GFR induced by ANP. Prazosin did not modify the renal effects of ANP. These results suggest that the natriuretic effect of ANP is inhibited by agents that increase cyclic AMP in vascular smooth muscle cells. It is also suggested that the natriuretic effects of ANP can be explained by an increase in GFR and changes in intrarenal hemodynamics, rather than by the direct effect of ANP on renal tubules.

Animals↗
PubMed1987

Effects of atrial natriuretic peptide, dopamine, and ouabain on aldosterone synthesis.

This study was undertaken to examine the effects of atrial natriuretic peptide (ANP), dopamine, and ouabain, which each are considered to be a kind of natriuretic factor, on aldosterone synthesis in vivo and in vitro. In the in vivo experiments, during infusion of one of the natriuretic factors, ANP (64 pmol X min-1 X kg-1), dopamine (20 nmol X min-1 X kg-1) or ouabain (684 II pmol x min-1 x kg-1), the stimulatory action of angiotensin (20 pmol X min-1 X kg-1) or adrenocorticotropin (ACTH, 7 pmol X min-1 X kg-1) on aldosterone synthesis was investigated in 36 anaesthetized (pentobarbital, 40 mg/kg, iv) female rabbits. In the basal condition, aldosterone synthesis was suppressed slightly by each of the natriuretic factors. The stimulatory actions of angiotensin II and ACTH on aldosterone synthesis were significantly attenuated by pre-treatment with ANP and dopamine. However, ouabain infusion did not induce any changes in the synthesis of aldosterone, 18-hydroxycorticosterone (18-OHB), and corticosterone (B) in either the basal or the stimulated conditions. For the in vitro experiments, rabbit adrenal glomerulosa cells (10(5) cells/tube) were used. The effects of ANP and dopamine on the aldosterone synthesis revealed results identical to those from the in vivo study. However, in contrast to the in vivo study, ouabain completely inhibited the synthesis of aldosterone, 18-OHB and B. The above results obtained in vivo and in vitro suggest that ANP inhibits corticosterone methyloxidase II activity and dopamine inhibits corticosterone methyloxidase I activity. However, from the present study we were unable to specify the action of ouabain on the synthesis of aldosterone and its related substances.

18-Hydroxycorticosterone↗
PubMed1987

Pre-operative evaluation of the prognosis of hypertension in primary aldosteronism owing to adenoma.

The prognosis of hypertension was evaluated pre-operatively in 40 patients with primary aldosteronism owing to adenoma by examining the severity of hypertension, family history of hypertension, age of the patients, duration of hypertension, plasma renin activity, plasma aldosterone concentration, and efficacy of spironolactone (100 mg per day for 10 days) on blood pressure. In 30 of the 40 patients, the blood pressure was reduced to below 160/95 mmHg within a year after adrenalectomy (responders). In the other 10 patients, the blood pressure was not markedly reduced and remained above 160/95 mmHg (nonresponders). There were no significant differences in the age of the patients, family history of hypertension, plasma renin activity or plasma aldosterone concentration between these two groups. The severity of hypertension as judged by the WHO classification and the duration of hypertension prior to operation seemed to be of some use in assessing the postoperative prognosis of hypertension, but the efficacy of spironolactone was far more useful. That is to say, a reduction in mean blood pressure of more than 15 mmHg after administration of spironolactone was observed in 29 of the 30 responders. The remaining one patient showed an 11 mmHg reduction in mean blood pressure. On the other hand, none of the nonresponders revealed a reduction in mean blood pressure of more than 15 mmHg after spironolactone administration. From these results it is concluded that the pre-operative response of blood pressure to administration of 100 mg per day of spironolactone for 10 days represents a useful indicator of the postoperative prognosis of hypertension in patients with primary aldosteronism owing to adenoma.

Adenoma↗
PubMed1987

Angiotensin II-induced drinking in water-deprived and nephrectomized dogs.

We evaluated the dipsogenic effects of angiotensin II (Ang II) in relation to the steady-state level of the endogenous renin-angiotensin system (RAS) by measuring water intake in 22 trained dogs during three 20 min intravenous (i.v.) infusions of [Ile5] Ang II (10, 15 and 50 ng/kg/min). Measurements obtained in normally hydrated (NHyd) dogs were compared with those obtained in dogs pretreated as follows: 24 hr water deprivation (WD); WD combined with chronic blockade of the RAS (300 mg/day X 3 days of SQ 14225) (WD + SQ); and 48 hr after bilateral nephrectomy (BNX). Both WD and WD + SQ were given water before Ang II infusion. Plasma renin activity (PRA) and serum and CSF electrolytes (cisterna magna catheter) were measured. All treatments caused a significant (p less than 0.05) increase in CSF sodium (Na+) that was not paralleled by hypernatremia in BNX dogs (142 +/- 1 vs 144 +/- 1 mEq/L in NHyd). WD and WD + SQ caused a 2- and 12-fold increase in PRA, respectively; PRA was not detectable in BNX. Suppression of blood Ang II by WD + SQ produced a reduced latency and significant enhancement of the thirst behavior elicited by Ang II at all doses; however, i.v. Ang II did not elicit drinking in the WD state. Furthermore, in BNX, the same phenomenon as in WD + SQ was observed. These data are compatible with the concept that endogenous levels of Ang II play a key role in regulating drinking behavior. However, these findings do not negate the possibility that Ang II acts synergistically with CSF Na+, but not plasma Na+, to modulate drinking behavior.

Angiotensin II↗