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Biomedical subjects

T Saruta

Publications and source records attributed to T Saruta.

At least 397 records · Page 22Linked to original sources
PubMed1991

Role of vasopressin in salt-induced hypertension in baroreceptor-denervated uninephrectomized rabbits.

To elucidate the contributions of renal, humoral, and arterial baroreceptor reflex components to salt-induced hypertension, we administered 10% NaCl intravenously for 10 days to sinoaortic-denervated rabbits with unilateral nephrectomy (n = 7), sinoaortic-denervated rabbits with intact kidneys (n = 7), and sham-operated sinoaortic-denervated rabbits with unilateral nephrectomy (n = 7). Serial changes in mean arterial pressure (MAP), heart rate, and blood pressure variability were recorded. In sinoaortic-denervated rabbits with unilateral nephrectomy, MAP increased significantly from 109 +/- 2 to 124 +/- 3 mm Hg (day 4) and remained elevated for the rest of the experiment. This elevation of MAP was accompanied by a reduction in the standard deviation of MAP, with significant elevations in plasma vasopressin, norepinephrine, and atrial natriuretic peptide concentrations and in sodium retention. In the other groups, there were no significant changes in these vasoactive hormones. In the sham-operated sinoaortic-denervated rabbits with unilateral nephrectomy, sodium retention was similar to that of sinoaortic-denervated rabbits with unilateral nephrectomy. Continuous infusion (1 microgram/kg/hr) of a V1 antagonist prevented the elevation of blood pressure and plasma norepinephrine, the accumulation of sodium, and the reduction of blood pressure lability, whereas a bolus injection (10 micrograms/kg) on day 4 reduced blood pressure from 128 +/- 3 to 115 +/- 2 mm Hg (p less than 0.005). These results imply that vasopressin plays a crucial role in the expression of salt-induced hypertension in rabbits with compromised baroreceptor and renal function.

Animals↗
PubMed1991

Effect of isoproterenol on intracellular pH of the intercalated cells in the rabbit cortical collecting ducts.

To examine the mechanisms which regulate the functions of the intercalated cells (ICs) in the cortical collecting duct (CCD), the effect of isoproterenol on intracellular pH (pHi) of ICs was studied with the in vitro microperfused rabbit CCD, using the single cell pHi determination technique with fluorescent dye, 2',7'-bis-(2-carboxyethyl)-5(and-6)carboxyfluorescein. The pHi of beta-IC was significantly decreased with the addition of basolateral 10(-6) M isoproterenol (7.21 +/- 0.04 to 7.05 +/- 0.04), whereas alpha-IC did not show any change. This response of beta-IC to isoproterenol was dose-dependent and completely inhibited by the beta-blockers, atenolol or propranolol. The addition of forskolin or 8-Br-cAMP mimicked the effects of isoproterenol, suggesting that the activation of adenylate cyclase induced the decrease in pHi. The rate of pHi changes after the Cl- removal from the perfusate, which is considered to reflect the activity of luminal anion exchanger, was significantly higher with isoproterenol (0.032 +/- 0.009 pH unit/s) than that in the control (0.023 +/- 0.009 pH unit/s). The present studies provide direct evidence for the regulation of beta-IC function by beta-adrenergic receptor; and the luminal Cl-/HCO3- exchanger was considered to be stimulated by beta-agonist, directly.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Effect of L-dopa in young patients with hypertension.

The effects of L-dopa on blood pressure, heart rate, plasma renin activity, norepinephrine, epinephrine and prolactin were studied in a randomized single-blind trial in 36 patients with essential hypertension. In response to L-dopa, 250 mg administered orally, the blood pressure decreased significantly as compared with the results of placebo treatment. The heart rate and plasma norepinephrine and epinephrine were unchanged. The plasma renin activity and prolactin decreased as a result of L-dopa administration. The administration of a peripheral DA2 dopamine receptor blocker, domperidone (20 mg, orally) prevented the L-dopa-induced reduction in plasma prolactin but failed to block the fall in blood pressure and plasma renin activity. These results suggest that the blood pressure-lowering effect of L-dopa may be mediated through multiple sites involving D1 dopamine receptors, the central nervous system, and the renin-angiotensin system.

Adult↗
PubMed1991

Regulation of aldosterone synthase cytochrome P-450 in rat adrenals by angiotensin II and potassium.

Changes in the levels of aldosterone synthase cytochrome P-450, a recently identified enzyme in rat adrenals, were studied in response to the renin-angiotensin system and K stimuli. As examined by an immunoblot technique, the zona glomerulosa mitochondria from rats fed on a low Na-normal K diet (8.6 mmol Na+ and 207 mmol K+/kg of diet) or a low Na-high K (0.2 M KCl in drinking water) diet for 4-10 days contained significantly higher amounts of aldosterone synthase cytochrome P-450 than those from rats fed on a normal diet (86 mmol Na+ and 207 mmol K+/kg of diet). Activities of the enzyme were also found to increase by about 10-fold on day 10. In concert with these changes, both plasma renin activity and plasma aldosterone concentration increased, indicating that the renin-angiotensin system was activated in these rats. Feeding with a normal Na-high K diet also induced significantly higher levels of both amount and activity of aldosterone synthase cytochrome P-450 together with an elevated serum K concentration on day 4, though they all decreased to near the control level on the following days. On the other hand, when enalapril malate, an angiotensin I-converting enzyme inhibitor, was administered to the low Na-normal K rats, the increases in the amount and activity of the enzyme as well as in plasma aldosterone concentration were suppressed altogether. However, the enalapril administration to the low Na-high K rats suppressed the increases only partially. These results indicate that the aldosterone synthase cytochrome P-450 is an ultimate target of the regulation of aldosterone biosynthesis by angiotensin II and K.

Angiotensin II↗
PubMed1991

Renin-dependency of glycyrrhizin-induced pseudoaldosteronism.

A prospective study was carried out on 12 patients with chronic hepatitis who were taking 546 mg/day of glycyrrhizin for 4 weeks in order to identify the factors responsible for the development of hypertension and hypokalemia. In 5 patients, blood pressure increased and serum potassium decreased after the treatment (responders). In the remaining 7 patients, these values were unchanged (nonresponders). There were no significant differences in age, plasma aldosterone, the catecholamine concentrations or serum transaminases. The basal plasma renin activity (PRA) in the responders was more than 1.5 ng/m/h (2.5 +/- 0.3 ng/m/h), while that in the non-responders was less than 1.5 ng/m/h (0.7 +/- 0.1 ng/ml/h). Furthermore, a positive correlation between the basal RPA and the changes in blood pressure, and a negative correlation between the basal PRA and the changes in potassium were found. These results suggest that patients with higher PRA levels are more likely to develop hypertension and hypokalemia when treated with glycrrhizin.

Adult↗
PubMed1991

Effects of routine heparin therapy on plasma aldosterone concentration.

Changes in plasma aldosterone, plasma renin activity, plasma cortisol, serum sodium and potassium concentrations were studied in 9 patients with thromboembolic diseases treated with heparin. Heparin was administered at doses of 700-1000 units/h for 7-10 days. Plasma aldosterone decreased from 239 +/- 33 to 114 +/- 25 pmol/l during heparin therapy and returned to basal levels after discontinuation of the therapy. In addition, responses to a low sodium intake (3 g/day) and ACTH were examined in 5 patients during and 2 weeks after heparin therapy. The increase in plasma aldosterone caused by low sodium intake was significantly attenuated during heparin therapy (124 +/- 5% increase from baseline) as compared with that 2 weeks after heparin therapy (148 +/- 7%, p less than 0.05). On the other hand, ACTH stimulated plasma aldosterone similarly during and at 2 weeks after heparin therapy (increase from baseline: 190 +/- 20% vs 193 +/- 9%). These results suggest that heparin decreased plasma aldosterone owing to attenuation of the angiotensin II-induced aldosterone production.

Adrenocorticotropic Hormone↗
PubMed1991

Calcitonin gene-related peptide modulates adrenal hormones in conscious dogs.

The effects of a small dose (2 pmol/kg) of human calcitonin gene-related peptide I on plasma renin activity and hormones, including, aldosterone, ACTH, cortisol, AVP and ANH, were investigated in 14 conscious dogs. In addition, we studied the effects of calcitonin gene-related peptide on aldosterone secretion when it is stimulated by angiotensin II and ACTH. An intravenous bolus injection of 2 pmol/kg of calcitonin gene-related peptide raised plasma renin activity (by 216%, p less than 0.05), ACTH (by 85%, p less than 0.05), AVP (by 89%, p less than 0.05), and ANH (by 36%, p less than 0.05). Despite the elevation of plasma renin activity, aldosterone was decreased (by 52%, p less than 0.05). Cortisol did not change significantly. Infusion of 1 pmol.kg-1.min-1 of angiotensin II produced an elevation of aldosterone (by 186%, p less than 0.01), which was completely inhibited by pretreatment with an injection of 2 pmol/kg of calcitonin gene-related peptide. On the other hand, aldosterone secretion stimulated by ACTH was not altered significantly by pretreatment with an injection of 2 pmol/kg of calcitonin gene-related peptide. These results suggest that calcitonin gene-related peptide inhibits aldosterone secretion, especially when aldosterone is stimulated by angiotensin II. In addition, calcitonin gene-related peptide may be involved as an endocrine modulator in the physiological control of other several hormones closely related to the hemodynamics.

Adrenal Cortex Hormones↗
PubMed1991

Characterization of alterations of hemodynamics and neuroendocrine hormones in dexamethasone induced hypertension in dogs.

The serial changes in systemic and renal hemodynamics, water and electrolyte balances and various vasoactive hormones were examined in 12 conscious dogs before, during (10 days) the administration of dexamethasone (DEX: 0.5 mg/kg/day) and after the cessation of DEX. In addition, during the administration of DEX, pressor responses to angiotensin II, norepinephrine, an angiotensin II analogue, saralasin, and an alpha-1-blocker, prazosin, were studied. Abrupt elevation of blood pressure to 106 +/- 5 mmHg on Day 1 (vs. 91 +/- 6 mmHg control: P less than 0.05) associated with marked increases in total peripheral resistance (P less than 0.01) was shown in DEX treated animals. Accompanied with these changes, renal blood flow increased to 146 +/- 12 ml/min (vs. 103 +/- 8 ml/min control: P less than 0.05) on Day 1 and maintained. In contrast, the results of serial alterations in hormones could not show any significant changes except significant elevations in atrial natriuretic peptide and reductions of cortisol and arginine vasopressin. Also, marked natriuresis and diuresis were observed in DEX administration dogs. Pressor response to norepinephrine was significantly increased and administration of either saralasin and prazosin significantly reduced the blood pressure of DEX treated animals. These results in DEX-treated conscious dogs confirmed our previous findings in human and rats. Glucocorticoid-induced hypertension mainly depends on the increases in total peripheral resistance but not volume factors.

Animals↗
PubMed1991

The role of sex hormones and sodium intake in postmenopausal hypertension.

To determine the role of sex hormones and sodium intake in hypertension seen in postmenopausal woman, 12 women (aged 50 to 59 years) in whom blood pressure increased for the first time to above 150/90 mmHg after cessation of menstruation were examined in comparison with 7 age-matched postmenopausal normotensive women (118 +/- 2/62 +/- 3 mmHg). All subjects were admitted to the hospital and their sodium intake was maintained at 204 (normal), 306 (high), and 51 (low) mmol/day for 5 days each. In each period, body weight, blood pressure, heart rate, serum levels of sex hormones and vasoactive hormones, and urinary excretions of sodium, kallikrein and dopamine were determined. The plasma levels of prolactin, progesterone, oestrone, and oestradiol in the hypertensive women were all significantly lower than those in the normotensive women in all study periods. With a change in sodium intake from high to low, blood pressure in 8 out of 12 hypertensive patients decreased by more than 10% from 160 +/- 2/100 +/- 2 mmHg to 144 +/- 2/87 +/- 2 mmHg, while in the normotensive women, only 1 out of 7 patients responded to this change in sodium intake. The changes in sodium intake did not alter the plasma levels of sex hormones in the hypertensive and normotensive subjects. Among the hypertensive patients, three had a history of pregnancy-induced hypertension, while none of the normotensive subjects had such a history. The results of the present study suggest that decreases in sex hormones and increased sensitivity to sodium are important factors in the genesis of postmenopausal hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1991

The suppressive effect of anti-asialo GM1 antibody on low-dose streptozotocin-induced diabetes in CD-1 mice.

To elucidate the role of natural killer (NK) cells in the pathogenesis of diabetes in streptozotocin-induced diabetes, we examined whether treatment with anti-asialo GM1 antibody prevents the occurrence of diabetes in CD-1 mouse model. Anti-asialo GM1 antibody was injected intraperitoneally 2-3 times a week starting three days before the first streptozotocin injection. In controls, rabbit immunoglobulin or saline was injected instead of anti-asialo GM1 antibody. Three of twelve anti-asialo GM1 antibody-treated mice developed diabetes, however eight of eight (100%) rabbit immunoglobulin injected mice and 20 of 23 saline-injected mice developed diabetes. The incidence of diabetes in the anti-asialo GM1 antibody-injected group was significantly higher than in the two control groups (p less than 0.01, p less than 0.01, respectively). The NK-cell activities of spleen cells from anti-asialo GM1 antibody-treated mice were significantly lower than in control mice. Flow-cytometry analysis demonstrated that anti-asialo GM1 antibody-positive cells had disappeared from spleens of anti-asialo GM1 antibody-injected mice but no suppression of T-lymphocytes could be demonstrated. These results suggest that NK cells play a role in the pathogenesis of streptozotocin-induced diabetes in CD-1 mice.

Animals↗
PubMed1991

Angiotensin II stimulates collagen synthesis in cultured vascular smooth muscle cells.

The aim of the present study was to investigate whether angiotensin II, by increasing extracellular matrix synthesis, contributed to the vascular wall thickening observed in hypertension. Thus, we examined the direct effects of angiotensin II on collagen and fibronectin synthesis in cultured rat vascular smooth muscle cells by measuring 3H-proline incorporation. Angiotensin II, in a concentration of 10 mumol/l, increased collagen synthesis in a dose-dependent manner up to 1.8-fold. This increase occurred within 24 h after the addition of angiotensin II and the time required to reach maximum stimulation was approximately 48 h. This increase was receptor-mediated and correlated with an increase in its specific messenger RNA. A closer study of the collagen increase demonstrated a relatively greater increase in type V collagen than type I or type III collagen. Fibronectin synthesis was also increased 1.5-fold with 10 mumol/l angiotensin II. These data suggest that angiotensin II induces vascular wall thickening by acting directly on smooth muscle cells and enhancing the production of extracellular matrix proteins.

Angiotensin II↗
PubMed1990

Effect of growth hormone on rat hepatic cytochrome P-450f mRNA: a new mode of regulation.

Growth hormone (GH) is known to be involved in the control of rat hepatic drug and steroid metabolism through its action on cytochrome P-450s. To examine the role of GH in the regulation of cytochrome P-450f (P-450f), a full-length cDNA clone corresponding to P-450f was isolated and the 3'-non-coding region was utilized for Northern and slot-blot analyses. P-450f mRNA levels were low in neonates, increased after age 4 weeks in male and female rats, and were approximately 3 times higher in the liver of adult female rats than male rats. Hypophysectomy caused a significant decrease in P-450f mRNA levels in male and female rats. Intermittent injection with human growth hormone (hGH) to mimic the male secretory pattern of GH caused a 9-fold increase in P-450f mRNA in hypophysectomized male rats to levels near male control levels, whereas continuous administration of hGH to mimic the female secretory pattern caused a greater increase in P-450f mRNA levels in male and female hypophysectomized rats (25-fold and 9-fold respectively) to levels nearer female control levels. The responses of the other GH-stimulated P-450s, P-450-male and P-450-female, to the different modes of hGH treatment were different from that of P-450f. Since sex hormones are known to affect the regulation of other P-450s, the effect of sex hormones on P-450f mRNA was studied. Ovariectomy caused a 2.4-fold reduction in P-450f mRNA which was partially reversed by estradiol treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Efficacy and safety of carvedilol in renal hypertension. A multicenter open trial.

Carvedilol, a novel beta-blocker with a vasodilating action, was given either alone (monotherapy) or with diuretics (combination therapy) to 42 patients with renal hypertension. The hypotensive effect, safety, and optimal dose were investigated. In all, 23 untreated patients (16 men and 7 women; average age, 56.4 +/- 2.5 years) made up the monotherapy group and 19 diuretic-treated patients (11 men and 8 women; average age, 56.4 +/- 2.5 years) comprised the combined therapy group. All subjects had an initial blood pressure (BP) of greater than 160/95 mmHg and were started on 5 mg/day oral carvedilol. The dose was gradually increased to a maximum of 20 mg/day, or until either the BP was reduced to less than 149/89 mmHg or the reduction in mean BP was greater than 13 mmHg compared with baseline levels. The total study period was 8 weeks. With monotherapy, the BP and heart rate decreased significantly from 167/102 to 150/94 mmHg and from 81 to 74 beats/min, respectively. With combined therapy, the BP and heart rate fell significantly from 176/103 to 142/85 mmHg and from 81 to 70 beats/min, respectively. Responders were defined as subjects with a BP of less than or equal to 149/89 mmHg or those showing a fall of greater than or equal to 13 mmHg in mean BP. Responders accounted for 52.2% of the monotherapy group and 73.6% of the combination therapy group. Orthostatic hypotension was not seen in either group. Serum creatinine and blood urea nitrogen (BUN) levels were not altered by administration of carvedilol. Dizziness was noted by 1 of the 23 subjects in the monotherapy group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1990

Comparison of clinic and home blood pressure levels and the role of the sympathetic nervous system in clinic-home differences.

Plasma and urine norepinephrine, epinephrine and home blood pressure were measured in 48 young hypertensive men (mean age, 21 years) and 25 matched normotensive controls. Plasma samples were drawn following 30 min rest in the clinic and 24 h urine samples were collected at home. Twenty-one hypertensive patients were given a single dose of clonidine (150 micrograms orally). Changes in blood pressure, heart rate and plasma norepinephrine were assessed. Twenty-five of the hypertensive patients were found to have a normal home blood pressure (defined from records of the normotensive subjects). The other group of patients maintained a high home blood pressure. In comparison to normal subjects, patients with a high home blood pressure were characterized by higher urinary norepinephrine and epinephrine excretion and higher plasma epinephrine. Patients with a normal home blood pressure had normal heart rate at home, normal plasma and urinary catecholamines. However, the two groups of hypertensives could not be distinguished on the basis of clinic blood pressure, plasma or urinary catecholamines due to considerable overlap. At 90 min after oral clonidine administration, the plasma norepinephrine and blood pressure levels were decreased in both groups of hypertensives to a similar extent. The changes in heart rate were significantly smaller in patients with a high home blood pressure than in those with a normal home blood pressure. These results suggest that the patients with a high home blood pressure tended to have a high sympathetic nerve activity. However, the two groups of hypertensives could not be separated on the basis of plasma or urinary catecholamine measurements.

Administration, Oral↗
PubMed1990

Cytophagic histiocytic panniculitis evolving into total lipodystrophy.

A 15-year-old boy had persistent fever with severe neutropenia, thrombocytopenia, coagulation disorder, and marked elevation of lactate dehydrogenase values. A diagnosis of cytophagic histiocytic panniculitis was made after repeated skin biopsies. Three years after onset, he gradually lost 20 kg in body weight, and both skin and bone marrow specimens revealed degenerative changes of fatty tissue without any inflammatory cells. These findings suggest that total lipodystrophy syndrome results from the inflammatory destructive process of adipose tissue. To our knowledge, our report is the first to show, in a series of histologic studies, that an inflammatory destructive process may be involved in some cases of total lipodystrophy syndrome.

Adolescent↗