Nagao Kajiwara

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 μ/day) and CD20 (127±11 μg) than the poor responder group (89±6 μ/day and 79±13 μ, respectively). During the low calorie period, both UNE (87±15 μg/day) and CD20 (74±10 μ) 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<0.05). In conclusion, suppression of sympathetic activity plays a role in blood pressure reduction during moderate caloric restriction.

Left ventricular geometric patterns and QT dispersion in borderline and mild hypertension: their evolution and regression.

To investigate whether QT dispersion increases in borderline and mild hypertension during a longitudinal observation of > 3 years and whether it is improved with medications, left ventricular geometric patterns and QT dispersion were studied with special regard to their longitudinal changes in 85 male borderline and mild hypertensive subjects with left ventricular mass index < 125 g/m2. These subjects were followed for > 3 years without medication. Thirty-two patients with a left ventricular mass index > 125 g/m2 at the end of follow-up period were further observed using antihypertensive drugs for an additional 3 years. Echocardiograms and electrocardiograms were obtained at the beginning and end of the follow-up period. At the end of the follow-up period, subjects were classified into four groups based on ventricular geometric patterns determined by left ventricular mass index and relative wall thickness in diastole. The QT dispersion was greater in patients with concentric hypertrophy (56+/-18 msec) than in patients with normal geometry (41+/-17 msec) (P < .05) and increased significantly in the former group during the follow-up period. After medication, the left ventricular mass index regressed and the QT dispersion decreased (from 55+/-21 to 50+/-26 msec, P < .01) in these patients. Thus, these findings suggest that changes in the QT dispersion reflect both concentric evolution and regression of left ventricular hypertrophy.

Prospective studies on left ventricular geometric patterns and exercise tolerance in unmedicated men with borderline and mild hypertension

Objective This study was designed and conducted to assess the clinical significance of left ventricular geometric patterns and physical fitness in subjects with untreated borderline and mild hypertension. Methods Symptom-limited maximal treadmill stress testings and echocardiographic examinations were administered to 192 previously unmedicated men. Left ventricular geometric patterns were determined by the combined criteria of left ventricular mass index and relative wall thickness.subject whose left ventricular mass index was <125 g/m2 were followed up for more than 3 years. Results Normalized treadmill time was lower and pressure rate products at peak exercise were higher in patients with concentric hypertrophy than in those with normal geometry. Of the 77 patients who revealed left ventricular mass index at baseline <125 g/m2 and who were successfully followed without medication for more than 3 years, 18 demonstrated concentric hypertrophy at the final follow-up examination. During the follow-up period, these 18 patients had significant further augmentation of concentric geometric features, significant decreases in both cardiac output and normalized treadmill time, and significant increases in casual blood pressure and total peripheral resistance compared with those at baseline. Conclusion Patients with concentric hypertrophy exhibited slightly but significantly impaired levels of physical fitness and cardiac work efficiency, and the progression of concentric hypertrophy demonstrated further impairments of these conditions. Therefore, not only lowering blood pressure, but also improving left ventricular hypertrophy, cardiovascular hemodynamics, and physical fitness might be required in patients with concentric hypertrophy.

The Relationship of Hyperinsulinemic State to Left Ventricular Hypertrophy, Microalbuminuria, and Physical Fitness in Borderline and Mild Hypertension

The relationship of the hyperinsulinemic state to left ventricular hypertrophy, left ventricular geometric patterns, microalbuminuria, and physical fitness were studied in 52 middle-aged unmedicated men with borderline and mild hypertension. Left ventricular mass index and relative wall thickness were assessed by echocardiography. Physical fitness was determined by symptom-limited maximal treadmill stress testings. The urinary concentration of microalbumin and C-peptide was measured in 24-h urine samples by radioimmunoassey. The 24-h urinary C-peptide excretion rate was correlated with left ventricular mass index (r = 0.46), relative wall thickness (r = 0.41), treadmill time (r = -0.35), normalized treadmill time (r = -0.52), systolic blood pressure at peak exercise (r = 0.29), and 24-h urinary microalbumin excretion (r = 0.48). Stepwise multiple regression analysis identified the left ventricular mass index, the 24-h urinary albumin excretion, and the normalized treadmill time as variables in the equation for the 24-h urinary C-peptide excretion. Thus, the hyperinsulinemic state is related to left ventricular hypertrophy, microalbuminuria, and impaired physical fitness in patients with borderline and mild hypertension.

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

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.

The Role of the Sympathetic Nervous System and Adrenals in Hemodynamic Changes after Intracerebroventricular

: 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.

高血圧自然発症ラットにおける脳室内angiotensin II投与による血圧, およびvasopressinの変化に対するセロトニン作動神経系の関与

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.

Effects of Chronic Atenolol Therapy on Cardiovascular Response to Isometric Exercise in Essential Hypertension

Cardiovascular response to 2 min of isometric handgrip exercise at 50% of maximum voluntary contraction was studied echocardiographically in 10 essential hypertensives, before and during treatment with atenolol for a mean of 2 months. The patients responded with increases in heart rate, systolic and diastolic blood pressures, cardiac output and calculated triple product, no changes in stroke volume and total peripheral resistance, and decreases in ejection fraction, mean velocity of circumferential shortening and mean diastolic posterior wall velocity of the left ventricle before treatment. Chronic atenolol therapy attenuated the increases in heart rate, blood pressure and triple product, and the decreases in ejection fraction, mean velocity of circumferential shortening and mean diastolic posterior wall velocity of the left ventricle but resulted in a marked increase in total peripheral resistance. The pressure response and triple product rise in response to isometric handgrip exercise were also decreased. This suggests an obvious advantage to hypertensive patients who may, therefore, be protected from the risk of cardiovascular complications following isometric exercise.

The Effects of the Intracerebroventricular Administration of Cimetidine on Hemodynamics in Conscious Rats

Histamine H2-receptor antagonists administered into the central nervous system have been shown to increase arterial pressure (AP) in anaesthetized animals (Paakkari et al., 1982). Few studies have been reported on the effects of centrally administered cimetidine (CIM), one of the histamine H2-receptor antagonists, in conscious animals. However, the mechanism of the pressor action of histamine H2-receptor antagonists remains unclear. The present study was designed to investigate the hemodynamic effects of intracerebroventricular (i.c.v.) CIM and the interaction between the sympathetic nervous system and histamine receptor system in conscious rats. Male Wistar rats weighing 200 gr were prepared for the experiment under a conscious and minimally restricted state. Five micrograms of i.c.v. saline (SAL-ICV group, n = 5) did not produce significant changes in mean arterial pressure (MAP) or heart rate (HR) (MAP from 85.6 +/- 3.4 to 86.0 +/- 4.3 mmHg and HR from 395.0 +/- 13.9 to 395.2 +/- 8.2 bpm, respectively). Twenty micrograms of i.c.v. phenoxybenzamine (POB-ICV group, n = 6) decreased MAP from 95.8 +/- 4.1 to 85.2 +/- 3.1 mmHg, -10.7 +/- 2.2 mmHg as delta MAP, and increased HR from 392.5 +/- 8.5 to 435.3 +/- 13.9 bpm, +42.8 +/- 6.8 bpm as delta HR. Two-hundred micrograms of intravenous (i.v.) POB (POB-IV group, n = 5) also decreased MAP from 96.0 +/- 4.3 to 71.0 +/- 5.1 mmHg, -25.0 +/- 2.7 mmHg as delta MAP, and increased HR from 395.8 +/- 10.5 to 473.0 +/- 12.4 bpm, +77.2 +/- 7.6 bpm as delta HR. The changes in MAP and HR were much greater in the POB-IV group than those in the other two groups. The subsequent i.c.v. administration of 250 micrograms of CIM induced an increase in MAP (+19.4 +/- 1.7 mmHg as delta MAP) and a decrease in HR (-36.4 +/- 3.1 bpm as delta HR) in the SAL-ICV group, which continued for at least 30 minutes producing peak effects 2 minutes after i.c.v. administration of CIM. However, an elevation of MAP caused by i.c.v. CIM was much more inhibited in the POB-ICV group than in the POB-IV group (+2.5 +/- 0.7 mmHg as delta MAP in the POB-ICV group and +5.0 +/- 1.3 mmHg as delta MAP in the POB-IV group, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)