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Biomedical subjects

N Sano

Publications and source records attributed to N Sano.

At least 127 records · Page 7Linked to original sources

Renal sympathetic responses to changes in arterial pressure in conscious rabbits.

Renal sympathetic nerve activity (RSNA) at rest and in response to changes in mean arterial pressure (MAP) were examined by measuring norepinephrine (NE) spillover rate across the kidney in 14 conscious rabbits. NE spillover rate was calculated from veno-arterial difference in plasma NE concentrations across the kidney corrected by the fractional extraction of infused tritiated NE. Renal NE spillover rate (mean +/- S.E.M.) at rest in 14 conscious rabbits was 14.7 +/- 0.9 ng/min. During sodium nitroprusside infusions at 10 and 20 micrograms/kg/min, renal NE spillover rate significantly increased by 55 and 101% in response to falls in MAP of 15 and 19% respectively. During phenylephrine infusion at 2 micrograms/kg/min, renal NE spillover rate significantly decreased by 40% in response to a 14% rise in MAP. The relative contribution of renal to total NE spillover rate decreased during sympathetic stimulation, while this ratio was unchanged during sympathetic inhibition. This study demonstrates that the renal NE spillover method is sufficiently sensitive and reliable to detect the responses in RSNA to physiological stimuli in conscious rabbits. The difference observed in the degree of stimulation of renal versus total NE spillover rate during hypotension produces confirmation that sympathetic responses are not uniformly distributed in the body.

Animals↗

Renal sympathetic nerve activity measured by norepinephrine spillover rate in response to changes in blood pressure in conscious rabbits.

1. Renal sympathetic nerve activity (RSNA) in response to changes in mean arterial pressure (MAP) was examined by measuring renal norepinephrine (NE) spillover rate in conscious rabbits. 2. A chronic renal vein catheter was implanted for sampling renal venous blood without stress in conscious animals. 3. RSNA estimated by renal NE spillover rate significantly increased in response to moderate falls in MAP produced by sodium nitroprusside (SNP) infusion and decreased in response to moderate rises in MAP produced by phenylephrine (PE) infusion. 4. The NE spillover method is sufficiently sensitive to detect responses of RSNA to physiological stimuli in conscious rabbits.

Animals↗

A sympathetic component of baroreflex function in patients with essential hypertension.

1. The baroreflex-mediated changes in plasma norepinephrine (NE) and heart period (RR interval) to phenylephrine (PE)-evoked pressor and nitroprusside (NP)-evoked depressor stimulations were studied in 19 patients with chronic essential hypertension, 12 with borderline hypertension and in 11 age-matched normal controls. 2. Intravenous infusion of PE at a rate of 0.25-1.0 microgram/kg/min induced dose-related increases in mean arterial pressure (MAP) and in RR interval and a decrease in plasma NE. Similarly, NP infusion at a rate of 0.1-0.4 microgram/kg/min evoked the opposite changes in each variable. The reflex sensitivity was defined as the slope of linear regression between the changes in RR interval and MAP (RR/MAP) and between those in plasma NE (% of the baselines) and MAP (%NE/MAP). 3. Both RR/MAP and %NE/MAP for pressor and depressor stimulations were reduced below values found in normal subjects, in both chronic and borderline hypertensives. 4. The values of %NE/MAP was negatively related to the basal plasma NE during falls in blood pressure (r = -0.401, P less than 0.05). 5. The %NE/MAP may be a useful index of the sympathetic component of baroreflex sensitivity. A decrease in %NE/MAP in hypertensive and borderline hypertensive patients suggests a blunted sensitivity of the sympathetic constrictor reflexes.

Adult↗

Plasma free dopamine in human hypertension.

The concentration of plasma free dopamine (PDA) is said to be much lower than that of other catecholamines and its physiological significance remains unclear. Our recent studies using a newly developed radioenzymatic method disclosed the fairly distinctive features of PDA in patients with various types of hypertension. PDA was also confirmed as a variable responsive to postural change, dietary sodium loading and dopamine receptor antagonist. The results suggest that PDA could be a sensitive marker to represent the peripheral dopaminergic function, which might play an inherent role as a physiological regulator responsible for the cardiovascular and endocrine system.

Diet↗

Functional relationship between platelet alpha 2-adrenoceptors and sympathetic nerve activity in man.

Functional relationships between platelet alpha 2-adrenoceptors and sympathetic nerve activity were studied in patients with essential hypertension (n = 23), primary aldosteronism (n = 10), and normal subjects (n = 12). The maximum number of binding sites (Bmax) and the dissociation constant (Kd) of 3H-yohimbine on platelet membranes and resting plasma norepinephrine (NE) were similar among these groups of subjects. In all subjects combined, Bmax values were correlated positively (r = 0.471, p less than 0.01) to resting plasma NE and negatively (r = -0.531, p less than 0.01) to the changes in plasma NE when subjects were moved from lying to standing. A 2-4 week treatment with guanabenz or bethanidine induced a parallel fall of both Bmax and plasma NE, whereas administration of reserpine caused a similar fall of plasma NE but Bmax remained unchanged. Kd values were not changed after any of these treatments. The results support the view that platelet alpha 2-adrenoceptor density is functionally regulated in parallel with sympathetic nerve activity rather than plasma NE per se. This hypothesis seems quite reasonable when it is extended to the presynaptic alpha 2-adrenoceptors; otherwise, the negative feedback function on NE release should be lessened and contradictory to its physiological role.

Adult↗

[Effects of high sodium diet on dopaminergic mechanism in normal and hypertensive subjects].

To investigate the effects of dietary sodium on the peripheral dopaminergic mechanism, changes of unconjugated plasma dopamine(DA) and its related humoral factors were studied in 8 patients with essential hypertension(EH) and 8 age-matched normal controls(N) while they were receiving ordinary meals (Na, 130-180 mEq daily) followed by higher sodium (250-300 mEq daily) diets for a week. Plasma and urinary DA, norepinephrine(NE) and epinephrine(E) were measured by the highly sensitive COMT-mediated radioenzymatic procedure, which permits an accurate estimation of plasma DA as low as 5-6 pg/ml. Under high sodium diets, blood pressure and heart rate were not changed significantly in N and EH subjects. Urinary NE and E tended to decrease, while urinary DA increased significantly in both groups of subjects (p less than 0.05). There was a significant correlation between urinary sodium and DA (r = 0.590, p less than 0.001), but plasma DA failed to correlate significantly to urinary sodium or DA in all subjects. Plasma NE and E tended to decrease in both N and EH subjects, while plasma DA increased significantly (p less than 0.05) in EH from 7.2 +/- 0.8 pg/ml [mean +/- SEM] to 9.3 +/- 1.0 and slightly in N from 9.1 +/- 1.8 to 11.2 +/- 1.3. Plasma renin activity(PRA) and plasma aldosterone(PAC) were invariably decreased in all subjects, while plasma prolactin(PRL) remained unchanged. A significant correlation was observed between plasma DA and NE under ordinary meals (r = 0.733, p less than 0.01), but this correlation disappeared under high sodium diets. Plasma DA showed an inverse correlation to PAC (r = 0.351, p less than 0.05) under both dietary conditions. Upright posture induced a significant rise (p less than 0.05) in NE, E, DA, PRA and PAC with ordinary meals, but the responses of NE and PAC were apparently attenuated with high sodium diets. An intravenous injection of metoclopramide (MCP, 10 mg), a DA receptor antagonist, provoked a slight rise in plasma NE and DA with ordinary meals, of which responses were further enhanced with high sodium diets. MCP induced a definite rise in PAC and PRL in all subjects under both dietary conditions (p less than 0.01), while plasma E and PRA remained unchanged after MCP challenge. The results lend support to the view that unconjugated plasma DA could be a useful marker of peripheral dopaminergic activity, which might be a physiological regulator responsible for the suppression of aldosterone secretion and sympathetic nerve activity observed during high sodium intake.

Adult↗

A morphometric analysis of extracellular space in the developing spinal cord of the chick embryo.

The developmental changes in the amount and distribution of the expanded extracellular space (ECS) (i.e. wider than 100 nm) were analyzed in the cervical spinal cord of chick embryos between stage 9 and 29, using electron micrograph montages, which cover one half of the cross-sectional area of the cord. The percentage of the ECS expansion to the whole cross-sectional area of the cord was 11.0% at stage 9, 7.7% at stage 11, 7.8% at stage 15, and 9.7% at stage 17. It decreased markedly to 3.0% at stage 22 and 1.3% at stage 29. The highest percentage at stage 9 may reflect the dynamic structural changes associated with neural groove closure which takes place around this time. The marked decrease after stage 22 is associated with the rapid overall growth of the cord. Until stage 19, the ECS expansions were mostly elongated and arranged radially with respect to the central canal. The ECS became scarce and arranged randomly thereafter. Throughout the stages examined, especially between stages 17 and 19, percentage was higher in the outer half of the cord than in the inner half. The outer glial limiting membrane was not established by stage 29. Between stages 17 and 22, the percentage was higher in the dorsal region than in the ventral region. This appears to be associated with the regional difference in neuronal maturation. The first blood vessels penetrated the ventromedial portion of the cord around stage 22, where the ECS expansions were relatively scarce. The successive rapid decrease in the amount of ECS expansions can be correlated to the development of vascularization.

Animals↗

Lack of carcinogenicity of phenytoin in (C57BL/6 x C3H)F1 mice.

Groups of 50 B6C3F1 mice of each sex were given 0.012% or 0.006% phenytoin in their powdered diet for 78 wk and were then fed a basal diet for 8 wk. Control groups of 50 mice of each sex were fed powdered basal diet for 86 wk. Mean total intakes of phenytoin per mouse were 301 and 150 mg in males, and 292 and 154 mg in females, respectively. The survival rates of each group at week 86 were 72-86% in males, and 86-94% in females. Liver-cell tumors, alveolar tumors, and Harderian-gland adenomas in male mice, malignant lymphomas and/or leukemias in female mice, and a few tumors in other organs of both sexes were found. The total number of hepatocellular tumors in mice treated with the high dose of phenytoin was significantly smaller than that of control mice in males (p less than 0.05). However, hepatocellular carcinomas developed 15 to 3 wk earlier in a few mice of phenytoin-treated males than in the controls. In other organs, no significant increase of any particular tumor type was observed in the treated groups of both sexes. Thus, phenytoin was not carcinogenic in B6C3F1 mice in this study.

Administration, Oral↗

Histopathological and immunohistochemical studies on nickel sulfide-induced tumors in F344 rats.

Twenty-five tumors induced in F344 male rats were examined histologically and immunohistochemically using antibodies against myoglobin, myosin, desmin and cathepsin B. Eight were from rats which had been given intramuscular (im) injection and 17 were from rats which had been given subcutaneous (sc) injection of 5 mg of Ni3S2. Among 10 rhabdomyosarcomas, myoglobin was detectable in 3, myosin in 8, and desmin in all, but cathepsin B was present in none. Out of 8 malignant fibrous histiocytomas, cathepsin B was detectable in all, but the other antigens were absent. In a leiomyosarcoma, only desmin was detected. In two fibrosarcomas, none of the markers were detected. In four undetermined tumors, one reacted only with anti-desmin antibody, two with only anti-cathepsin B antibody, and one with none of the antibodies. Of the three myogenic markers utilized in this study, anti-desmin antibody appeared to be the most sensitive. Cathepsin B was found mainly in the histiocytic cells of malignant fibrous histiocytoma. Thus, desmin appears to be particularly valuable in distinguishing immature myogenic tumors from other primitive tumors, while cathepsin B is useful in distinguishing malignant fibrous histiocytoma from other pleomorphic mesenchymal tumors.

Animals↗

A plasma inhibitor of sodium and potassium activated adenosine triphosphatase in patients with essential hypertension.

The purpose of this study is to evaluate the plasma Na, K-ATPase inhibitor (NKI) in patients with essential hypertension and to compare the mode of its biochemical actions on the Na, K-ATPase with that of ouabain. Plasma NKI was extracted through a reversed-phase cartridge column and its inhibitory action on hog brain Na, K-ATPase was measured in vitro. Plasma NKI activity was significantly greater in patients with essential hypertension (44 +/- 2.8% (S.E.), n = 28, p less than 0.01) than in normotensive controls (25 +/- 2.4%, n = 21). No significant correlation was demonstrated between the values of plasma NKI and mean arterial pressure in either group. Both plasma NKI and ouabain showed a dose-dependent inhibition on the Na, K-ATPase reaction. An action of ouabain was competitively antagonized by increased concentration of potassium in the reaction mixture, while plasma NKI showed a constant inhibition on the Na, K-ATPase independently of potassium concentrations. The action of plasma NKI was of rapid onset and linear with time, while ouabain showed a delayed onset of the reaction over 30 sec, followed by a progressively increasing inhibition on the enzyme reaction. Finally, the inhibitory action of plasma NKI on Na, K-ATPase was completely abolished in the presence of bovine serum albumin even at the concentration of 500 micrograms/ml in the reaction mixture, which did not have any influence on the actions of ouabain. To sum up, the results showed a markedly different nature of plasma NKI from ouabain in the mode of biochemical actions on the Na, K-ATPase in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Assay of rat plasma pyruvate kinase activity with luciferin-luciferase.

An assay method for pyruvate kinase in rat plasma is described. Plasma samples were incubated with ADP and phosphoenolpyruvate in Tris buffer solution. The ATP produced by pyruvate kinase was measured by photocounting after the addition of a commercially available luciferin-luciferase preparation. Interference by ATP or adenylate kinase originally present in the sample was removed by a high degree of dilution. The assay is sensitive, reproducible, and rapid, especially when used for large numbers of samples. By this method, pyruvate kinase activity in normal rats was determined to be 0.51 +/- 0.05 (n = 6) U/ml plasma. In rats fed a vitamin E-deficient basal diet for 7, 10, or 14 weeks, pyruvate kinase activities were 0.70 +/- 0.11, 1.64 +/- 0.51, and 4.28 +/- 0.85 (n = 6) U/ml plasma, respectively. This method appears to be useful for the determination of pyruvate kinase activity in nutritional or pharmacological studies.

Animals↗

Induction of subcutaneous tumors in rats by 3,7- and 3,9-dinitrofluoranthene.

Two dinitrofluoranthenes (DNFs) derived from 3-nitrofluoranthene were purified to over 99%, and tested for tumorigenicity in F344/DuCrj male rats. Rats were inoculated s.c. with 0.05 mg 3,7- or 3,9-DNF twice a week for 10 weeks. All 21 rats given 3,7-DNF and 10 of 11 rats (91%) given 3,9-DNF developed tumors at the injection site by 48 weeks after the first injection. Twenty of the 21 tumors induced by 3,7-DNF and seven of the 10 tumors induced by 3,9-DNF were classified as malignant fibrous histiocytoma, but one tumor in the 3,7-DNF-treated group and three tumors induced by 3,9-DNF showed typical features of rhabdomyosarcoma. The first tumors in 3,9-DNF-treated rats appeared on day 88 (on day average 117), 10 weeks earlier than in 3,7-DNF-treated ones (on day average 186).

Animals↗