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Biomedical subjects

T Kushiro

Publications and source records attributed to T Kushiro.

At least 19 recordsLinked to original sources

Blood pressure response to hyperinsulinemia in salt-sensitive and salt-resistant rats.

We investigated the role of insulin in salt-sensitive hypertension in Dahl salt-sensitive and salt-resistant rats. The rats were kept in metabolic cages, and sodium intake and urinary sodium excretion were measured. In salt-sensitive rats receiving a 0.3% NaCl diet, sodium retention was significantly greater at weeks 1 and 2 in rats that received an insulin infusion than in those receiving a saline infusion. Mean arterial blood pressure and plasma norepinephrine levels were significantly higher at week 3 in insulin-treated rats than in saline-treated rats (mean arterial pressure, 137 +/- 3 mm Hg versus 119 +/- 3 mm Hg, p < 0.05; plasma norepinephrine, 0.40 +/- 0.02 ng/ml versus 0.27 +/- 0.01 ng/ml, p < 0.05). Insulin did not influence sodium retention, mean arterial pressure, or plasma norepinephrine in salt-resistant rats. Coadministration of an alpha-blocker (bunazosin, 10 mg/kg per day for 3 weeks) in salt-sensitive rats abolished the insulin-induced elevations in mean arterial pressure and sodium retention. When salt-sensitive rats were fed a low salt diet (0.03% NaCl), insulin did not raise mean arterial pressure. Thus, insulin elevated blood pressure only in the salt-sensitive model. The sympathetic nervous system and sodium retention in the early phase of insulin overload may contribute to elevation of mean arterial pressure in this model.

Animals

[Role of superoxide anion on onset and maintenance of hypertension in spontaneously hypertensive rats].

Endothelium-derived relaxing factor (EDRF) is a substance that is released by the vascular endothelium and mediates vasodilator responses induced by various substances including acetylcholine (AC). Superoxide anion (O2-) inactivates EDRF. It is well known that the endothelium-dependent vascular relaxations to AC are depressed in the aorta of spontaneously hypertensive rats (SHR). We studied the role of O2- on onset and maintenance of hypertension in SHR. Male 4- and 17-week old SHR (4SHR, 17SHR), and enalapril treated 17-week old SHR (5 mg/kg/day for 4 weeks: ETSHR), and age-matched normotensive Wistar-Kyoto rats (WKY; 4WKY, 17WKY) were used. Relaxation responses to AC or superoxide dismutase (SOD) were measured in isolated aortae from rats. Mean arterial pressure (MAP) was measured after injection of SOD in rats under conscious state. Systolic blood pressure of 4SHR, 17SHR, ETSHR, 4WKY, and 17WKY were 129 +/- 2 mmHg, 203 +/- 3 mmHg, 158 +/- 3 mmHg, 97 +/- 1 mmHg, and 138 +/- 2 mmHg, respectively. Although relaxation responses to AC were decreased in aortae from 4SHR, 17SHR, and ETSHR compared with those from age-matched WKY, relaxation responses to SOD dit not differ between SHR and corresponding WKY. Whereas the injection of SOD(10000 U/kg) elicited a significant reduction of MAP in 4SHR (-11 +/- 3 mmHg) and 17SHR (-24 +/- 5 mmHg), it has no effect in WKY. These data suggest that AC mediated endothelium-dependent relaxation is attenuated in SHR and that excessive O2- in the endothelium resulted from hypertension may contributes the decreased response in SHR.

Acetylcholine

Role of sympathetic activity in blood pressure reduction with low calorie regimen.

To investigate the effects of a low calorie regimen on sympathetic function and its relation to blood pressure response, 22 untreated obese essential hypertensive patients (50 +/- 2 years, body mass index 29 +/- 1 kg/m2) were hospitalized and a diet was prescribed of 2,000 kcal/day for 5 days (control period) followed by 800 kcal/day for 21 days without changing salt intake (8-10 g/day). The dose of intravenous phenylephrine infusion needed to elevate systolic blood pressure 20 mm Hg (CD20) and the 24-hour urinary excretion of norepinephrine (UNE) were measured. During the low calorie period, blood pressure normalized in 14 patients (responder group, 124 +/- 3/79 +/- 4 mm Hg) and eight remained hypertensive (poor responder group, 158 +/- 6/103 +/- 3 mm Hg). At the control period, blood pressure and body mass index were similar, but the responder group had higher UNE (134 +/- 15 micrograms/day) and CD20 (127 +/- 11 micrograms) than the poor responder group (89 +/- 6 micrograms/day and 79 +/- 13 micrograms, respectively). During the low calorie period, both UNE (87 +/- 15 micrograms/day) and CD20 (74 +/- 10 micrograms) decreased in the responder group; no change was seen in the poor responder group. Changes in UNE and systolic blood pressure were correlated (r = 0.6, p less than 0.05). In conclusion, suppression of sympathetic activity plays a role in blood pressure reduction during moderate caloric restriction.

Blood Pressure

[Role of the serotonergic nervous system in hemodynamic and vasopressin responses to centrally administrated angiotensin-II in spontaneously hypertensive rats].

The purpose of the study is to investigate the role of the serotonergic nervous system in centrally administrated angiotensin II (A-II) mediated hemodynamic as well as vasopressin (AVP) responses. Eight-week-old male SHR and age-matched Wistar Kyoto rats (WKY) were used and the experiment was performed in the conscious state. In protocol 1, after resting observation of 30 minutes 10ng of A-II was given intracerebroventricularly (i.c.v.). This was followed by i.c.v. injection of 1 microgram of 5-HT2 receptor antagonist, xylamidine, 50 minutes later; then 10ng of i.c.v. A-II was repeated after 10 minutes (SHR: n = 7, WKY: n = 10). In protocol 2, plasma vasopressin (AVP) was measured in the following groups. In one group, 1.3ml of blood was sampled from the carotid cannula after resting observation, and the same amount of blood from an age-matched donor rat of the same strain was transfused immediately. Two hours later, 10ng of A-II was given i.c.v., and blood was sampled again after 1 minute (SHR: n = 7, WKY: n = 12). In another group, 1 microgram of xylamidine was given i.c.v. and was followed by 10ng of A-II 10 minutes later; then blood was collected after 1 minute (SHR: n = 8, WKY: n = 13). In protocol 1, resting MAP were 144 +/- 6mmHg in SHR and 99 +/- 2mmHg in WKY. I.c.v. A-II elicited a consistent pressor response in both SHR and WKY, but the response was significantly larger in SHR than that in WKY, +45 +/- 3 and +37 +/- 1mmHg, respectively. Xylamidine had no effect on MAP, and repeated A-II produced significant pressor responses. However, the responses were significantly smaller in both SHR (+36 +/- 3mmHg) and WKY (+25 +/- 1mmHg) as compared with those to initial A-II injection. In protocol 2, resting AVP were similar in SHR (1.5 +/- 0.2pg/ml) and in WKY (1.6 +/- 0.1pg/ml). However, after i.c.v. A-II injection, AVP became higher in SHR (131 +/- 14pg/ml) than in WKY (64 +/- 6pg/ml). AVP after A-II injection with xylamidine pretreatment were similar in SHR (48 +/- 6pg/ml) and in WKY (45 +/- 4pg/ml). Since the responses of both MAP and AVP to i.c.v. A-II were larger in SHR, and the responses were effectively suppressed by S2 receptor antagonists, the central serotonergic nervous system may play an important role in the hemodynamic as well as AVP responses to i.c.v. A-II administration.

Angiotensin II

[Determination of the blood pressure level in mild hypertension. Significance of 20 minute resting blood pressure measurement comparing to 24 hour ambulatory blood pressure monitoring].

Determination of the blood pressure (BP) level in patients with mild hypertension (MHT) is quite difficult, since ulcerations of BP are tremendously exaggerated in the doctor's office. It has been well known that casual BP is less reliable to estimate LVH than BPs obtained at home or work-site. Although 24 hour ambulatory BP monitoring (ABPM) has been widely accepted to overcome this problems, it is still controversial whether this method is applicable to all hypertensive subjects with special regards to its cost and effect. Therefore, our study has dealt mainly with the development of more convenient and less expensive method to get reasonable BPs. Twenty two nonmedicated patients with MHT were selected for the study. After taking casual BP in the office, the resting 20 minute BP measurements at every 2 minute interval were performed with Dynamap 950. Ten BP values thus obtained were divided into two categorical phases; early and late. The mean systolic and diastolic pressures (Ps & Pd) in the early phase were significantly higher than those in the late phase. Beside mean Ps and Pd obtained from 24 hour ABPM, 4 categorical phases based on the time of a day were defined; morning (from awaking to noon), afternoon (from noon to 6 pm), evening (from 6 pm to bed time) and night (during sleeping). Mutual correlation coefficients of these categorical BPs were calculated and compared to identify reasonably high significant correlations. The results revealed the highest BP at the office and the lowest one during sleeping. The office BPs closely resembled to the ones during afternoon period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Studies on evaluation of the oxygen transport system function with multistage treadmill stress testing: comparison between normal control subjects and patients with coronary heart disease].

The oxygen transport system (OTS) function was evaluated with multistage treadmill stress testing on 171 normal control subjects and 80 patients with coronary heart disease (CHD). After Bruce's definition, OTS function was expressed with functional aerobic impairment (FAI), left ventricular impairment (LVI) or myocardial aerobic impairment (MAI), heart rate impairment (HRI) or chronotropic reserve impairment (CRI) and peripheral circulatory impairment (PCI). All subjects were monitored on heart rate, blood pressure, electrocardiogram and endtidal O2 and CO2 before and every one minute during the symptom limited maximal stress testing. Seventy three of 80 coronary patients were subjected to the coronary arteriography and were classified into four groups; 31 with single vessel disease (SVD), 20 with double vessel disease (DVD), 15 with triple vessel disease (TVD) and 7 with A-C bypass surgery. Comparison between normal control subjects and the CHD patients with regard to the relation of age and VO2max derived from the linear regression analysis disclosed the identical age-related decrease in VO2max in both groups. The age corrected VO2max in the CHD patients, however, was 2.2 METS less than that of normal control subjects. Therefore, the level of VO2max in CHD patients was determined not only by disease, but also by ageing process itself. Comparisons among three CHD groups with regard to FAI, LVI, HRI and PCI clearly demonstrated different functional impairments paralleling to the severity of the disease process. On the other hand, the patients with A-C bypass surgery revealed almost identical functional impairment to the patients with SVD. In conclusion, these simple and noninvasive evaluations of the oxygen transport system could give us valuable informations reasonably differentiating the clinical status of the patients with CHD.

Adult

[Effects of ketanserin on hemodynamic changes after intracerebroventricular corticotropin releasing factor administration in rats].

In order to elucidate the relation between the serotonergic nervous system and the hypothalamus-pituitary system in hemodynamic regulation, the effects of a serotonin S2 receptor antagonist, ketanserin, on hemodynamic changes after intracerebroventricularly (i.c.v.) administrated corticotropin releasing factor (CRF) were investigated. Male Wistar rats (n = 19) weighing approximately 200 g were used. Thirty minutes after either intravenous (i.v.) (KET-IV group) or intracerebroventricular (KET-IC group) administration of 100 micrograms of ketanserin, 10 micrograms of CRF was given i.c.v. and mean arterial pressure (MAP) and heart rate (HR) were observed for 40 minutes, which was followed by blood sampling for plasma norepinephrine (PNE). The experiment was performed under conscious state. Resting MAP and HR were similar in both groups. Neither i.v. or i.c.v. ketanserin alone induced significant changes in MAP and HR. Although there was consistent pressor responses (+10 +/- 1.7 mmHg) and increase in HR (+31 +/- 13 bpm) after CRF administration in KET-IV group, there was not significant changes in MAP (+17 +/- 1.0 mmHg) and HR (+4.3 +/- 5.7 bpm) in KET-IC group. PNE was significantly higher in KET-IV group than that in KET-IC group, 489 +/- 71 pg/ml and 179 +/- 57 pg/ml, respectively. These data suggest that the pressor response to i.c.v. CRF is related to the increased peripheral sympathetic tone, and that the central serotonergic nervous system may play an important role in the hemodynamic changes.

Animals

Prediction of the progression of cardiac hypertrophy in middle-aged mild hypertensives.

To investigate the predictive value of exercise tests and diastolic function measurements for the progression of left ventricular hypertrophy, symptom-limited treadmill stress testing and echocardiography were performed before and after a follow-up period of 3.5 years in 47 mild hypertensive men aged 42 +/- 2 years. The men were classified into three groups by the progression of the left ventricular mass index (%LVMI) during the observation, i.e. (LVMI after follow-up) - (LVMI before follow-up)/(LVMI before follow-up). The high-progression group (n = 13) had a %LVMI exceeding mean +/- 2/3s.d. of all subjects; the low-progression group (n = 21) had a %LVMI within mean +/- 2/3s.d. and the non-progression group (n = 13) had a %LVMI less than mean -2/3s.d. At the beginning of the observation, age, blood pressure at rest, LVMI, ejection fraction, mean velocity of circumferential fibre shortening, peak shortening rate and systolic time intervals (ET/PEP, ratio of ejection time to pre-ejection period) were similar among the three groups. However, the high-progression group showed a higher systolic pressure at peak exercise, a lower peak filling rate and a longer time to peak filling rate (TPFR) as corrected by the R-R interval of the ECG. These data suggest that systolic pressure at peak exercise and echocardiographically assessed diastolic function are useful in predicting the progression of cardiac involvement in mild hypertension.

Adult

Role of central serotonergic (5-HT2) receptor in blood pressure regulation in rats.

To investigate the role of the serotonergic nervous system in blood pressure regulation, 5 micrograms of 5-hydroxytryptamine (5-HT) was given i.c.v. before and after 1 microgram of i.c.v. xylamidine or 200 micrograms of i.c.v. ketanserin or 200 micrograms of i.v. ketanserin in conscious Wistar Kyoto rats. Also i.v. (0.5, 1, 2 micrograms) or i.c.v. (1 microgram) phenylephrine (PHE) were given before and after 1 microgram of i.c.v. xylamidine. I.c.v. 5-HT elicited a consistent pressor response of approximately 27mmHg and slight decrease in heart rate. MAP and heart rate did not change after xylamidine or ketanserin. Whereas pressor response to i.c.v. 5-HT after i.c.v. ketanserin or i.c.v. xylamidine was suppressed, it did not change after i.v. ketanserin. Neither i.c.v. nor i.v. PHE-induced pressor response was influenced by i.c.v. xylamidine pretreatment. These data suggest that the central 5-HT2 receptor may subserve pressor function in rats.

Amidines

[The effects of ketanserin on the hemodynamic response after intracerebroventricular administration of 5-hydroxytryptamine].

Recently, the serotonergic nervous system has been receiving attention, as it participates in the hemodynamic regulation as well as in the pathogenesis of hypertension. The purpose of this experiment is to investigate the role of the central and peripheral serotonergic receptor in the hemodynamic responses induced by intracerebroventricular (i.c.v) administration of 5-hydroxytryptamine (5-HT). Eight week-old male spontaneously hypertensive rats (SHR) and age matched Wistar Kyoto rats (WKY) were used, and the experiment was performed under conscious and minimum restrained states. Five micrograms of 5-HT was given i.c.v. followed by i.c.v. administration of 200 micrograms ketanserin. Mean arterial pressure (MAP) and heart rate (HR) were observed continuously for 30 minutes. Then 5 micrograms of 5-HT was given i.c.v. again in the same rat (SHR -IC group, n = 7; WKY-IC group, n = 7). The rest of the rats received 200 micrograms of ketanserin intravenously (i.v.) after i.c.v. administration of 5 micrograms 5-HT, and the same amount of 5-HT was given i.c.v. after the ketanserin i.v. (SHR-IV group, n = 7; WKY-IV group, n = 6). Five-HT elicited a significant pressor response in all groups of rats and a slight non-significant increase in HR. In SHR-IC group and WKY-IC group, neither ketanserin i.c.v. nor the second 5-HT i.c.v. administration caused significant changes in MAP and HR. In SHR -IV group, i.v. ketanserin caused a significant decrease in MAP (-8.8 +/- 1.4 mmHg), but no significant change in MAP in WKY-IV group (-1.1 +/- 1.2 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[The role of the sympathetic nervous system and adrenals in hemodynamic changes after intracerebroventricular administration of 5-hydroxytryptamine in rats].

Recently, the role of the serotonergic nervous system has been implicated in blood pressure regulation and in the pathogenesis of hypertension. However, the effects of 5-hydroxytryptamine (5-HT) administration on hemodynamics have been notoriously inconsistent and the precise mechanism of the blood pressure regulation of the serotonergic nervous system has not been elucidated yet. In our previous study, we demonstrated that the intracerebroventricular (i.c.v.) administration of 5-HT in rats elicited consistent pressor response with concomitant increase in plasma norepinephrine and that the pressor response was abolished by systemic pretreatment of phenoxybenzamine or by serotonin receptor antagonist, methysergide. The purpose of this experiment is to investigate further the relationship between the sympathetic nervous system and the serotonergic nervous system.

Adrenal Glands

[Effects of intracerebroventricular (I.C.V.) administration of 5-hydroxytryptamine (5-HT) on hemodynamics in conscious spontaneously hypertensive rats (SHR): relation to sympathetic nervous system].

UNLABELLED: Recently, the serotonergic nervous system has been receiving attention as part of the blood pressure regulating mechanism of the central nervous system, and it has been postulated that the system may participate in the pathogenesis of hypertension. The purpose of this experiment is to investigate the mechanism of hemodynamic change after i.c.v. administration of 5-HT in SHR and in normotensive Wistar Rats (WR). MATERIALS AND METHODS: Twenty-week-old male SHR (n = 11) and age-matched WR (n = 14) were used. On the day before the experiments, the unilateral carotid artery and jugular vein were cannulated. Also, a cannula was inserted stereotaxically into the anterior horn of the lateral cerebral ventricle. Experiments were performed under the conscious and minimum restrained state. Experiment I: After observation of resting mean arterial pressure (MAP) and heart rate (HR) for 20 minutes, 5-HT (5 micrograms/5 microliter saline) was administrated i.c.v., and MAP and HR were observed for 90 minutes. Then, 200 micrograms of phenoxybenzamine (POB) was given from the jugular cannula. Thirty minutes after the POB administration when MAP was stabilized, 5 micrograms of 5-HT was again given i.c.v., and MAP and HR were recorded for 30 minutes. Experiment II: Plasma norepinephrine (PNE) was measured before and 2 minutes after 5-HT i.c.v. administration. The control sample (1.5 ml) was withdrawn at least 30 minutes before the 5-HT injection, and immediately after the blood sampling, the same amount of blood which was obtained from the age-matched donor rat of the same strain was transfused. RESULTS: Experiment I: Resting MAP was 136.4 +/- 5.1 mmHg in SHR and 99.1 +/- 3.0 mmHg in WR. I.c.v. administration of 5-HT elicited consistent pressor response in SHR and in WR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals