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Biomedical subjects

E Miyajima

Publications and source records attributed to E Miyajima.

At least 19 recordsLinked to original sources

Transcription-reverse transcription concerted reaction and minimal residual disease in axillary sentinel nodes of breast cancer.

AIMS: To investigate the use of transcription-reverse transcription concerted reaction (TRC) to detect axillary lymph node metastases. METHODS: Metastases in 423 lymph nodes obtained from 50 breast cancer patients were investigated by routine pathological hematoxylin and eosin (H and E) staining and quantitative analysis of carcinoembryonic antigen (CEA) mRNA by TRC. Enhanced pathological studies, serial sectioning and immunohistochemistry were conducted for cases which were negative by routine pathology, but positive by TRC. RESULTS: Pathological examination identified metastatic disease in 67 lymph nodes. TRC CEA mRNA results were concordant with 89.8% of these cases at a threshold of 100 copies. TRC identified 30 false negative nodes, which was reduced to 15 by excluding node biopsies yielding less than 40 microg total RNA. Twelve nodes were histologically negative for cancer, but positive according to TRC. Serial sectioning and immunohistochemical analysis of these nodes revealed macrometastatic lesions in three, micrometastasis in one, and isolated tumor cells in two. CONCLUSION: TRC for the detection of CEA mRNA may complement routine pathological examination by sentinel lymph node biopsy (SNB) in early breast cancer. We have started an enhanced pathological examination with serial sectioning on all excised sentinel nodes to set the best threshold for the TRC method.

Adult↗

A new double cuff sphygmotonometer for accurate blood pressure measurement.

Accurate measurement of blood pressure (BP) is essential in the diagnosis and treatment of hypertension, but neither auscultatory nor oscillometric methods measure intra-arterial BP accurately in all circumstances. Algorithms for automatic BP-measuring devices differ from manufacturer to manufacturer, and no clear authorized algorithm criteria have yet been established. We have devised a double-cuff sphygmotonometer to measure BP on the basis of clear algorithms, and investigated the accuracy of this new method by comparing it with the photo-oscillometric method, which is the most accurate method for non-invasive measurement of intra-arterial BP. In the new method, a small cuff (3x6 cm) replaces the photo-sensor in the brachial cuff (13x24 cm) of the photo-oscillometric device, and BP is determined by means of the oscillation within the small cuff. The comparison based on procedures of AAMI-protocol was performed in 136 hypertensive patients and 54 normotensive subjects. The difference in systolic BP between the photooscillometric and double-cuff methods was -2.26+/-2.31 mmHg (89% under 5 mmHg), and the corresponding difference in diastolic BP was 1.9+/-2.50 mmHg (94% under 5 mmHg). In conclusion, we have devised a new double-cuff method which improves on the photo-oscillometric method, and although it seems to be less accurate than the photo-oscillometric method, the clarity of its algorithm makes it superior to the conventional oscillometric and auscultatory methods employing only one cuff.

Algorithms↗

Guanabenz combination therapy inhibits sympathetic nerve activity and regresses left ventricular hypertrophy.

The cardiovascular and sympatholytic effects of combination therapy with guanabenz were examined in 26 patients (48 +/- 13 years old [mean +/- SD]) with stage 2 and 3 hypertension. Included in the study were patients under treatment with conventional antihypertensive drugs whose systolic and diastolic blood pressure was above 140 and 90 mmHg, respectively. Blood pressure, heart rate, and sympathetic parameters such as plasma concentration of norepinephrine and muscle sympathetic nerve activity at rest as well as during ambulatory conditions, 24-hour urinary excretion of norepinephrine, and low frequency (LF: 0.04-0.15 Hz)/high frequency (HF: 0.15-0.4 Hz) power ratio as a marker of cardiac sympathetic activity during 24 hours were examined before and after guanabenz (4-8 mg/d) combination therapy with first-line antihypertensive drugs such as diuretics. Left ventricular mass index (LVMI) was also calculated by conventional echocardiography. After 32 weeks of guanabenz combination therapy, systolic and diastolic blood pressure, heart rate, plasma and urinary excretion of norepinephrine, muscle sympathetic nerve activity, and LF/HF power ratio were significantly decreased, while neither LF nor HF power was changed. LVMI was also significantly decreased (270 +/- 81 vs. 236 +/- 83 g/m2, p < 0.005). These results indicate that guanabenz combination therapy inhibits sympathetic nerve activity under resting conditions as well as during ambulatory conditions and may accelerate regression of left ventricular hypertrophy in patients with moderate to severe hypertension.

Antihypertensive Agents↗

Reduced sympathetic inhibition in salt-sensitive Japanese young adults.

The purpose of our study was to investigate the sympathetic response to excess salt loading of 54 normotensive young adults with and without a family history of hypertension. We examined muscle sympathetic nerve activity, plasma concentration and urinary excretion of catecholamines, and ambulatory blood pressures during low (4 g NaCl) and high (16 g NaCl) salt diet intake. Ambulatory blood pressure and urinary excretion of catecholamines are known to be reduced during sleep. These parameters were therefore calculated during waking and sleeping periods. The subject was defined as salt-sensitive when mean ambulatory systolic pressure during the waking period was > or =3 mm Hg higher during high salt intake than during low salt intake (n = 26: 21.4+/-0.3 years old). When mean systolic pressure was either lower or equal during high salt intake than during low salt intake, the subject was defined as salt-resistant (n = 24: 21.3+/-0.3 years old). Muscle sympathetic nerve activity, plasma concentration and urinary excretion of norepinephrine in salt-resistant subjects were significantly reduced (P<.05) by salt intake, whereas plasma concentration of epinephrine was unchanged and urinary excretion of epinephrine was reduced. In contrast, urinary excretion of epinephrine in salt-sensitive subjects was significantly elevated (P<.05) during high salt intake, whereas muscle sympathetic nerve activity and urinary excretion of norepinephrine remained unchanged despite a significant increase (P<.01) of ambulatory blood pressure. Of the salt-sensitive subjects, 73% (19 of 26) had a positive family history of hypertension, whereas only 5 of 24 salt-resistant subjects had a positive family history. These data indicate that the inhibition of sympathetic activity during a high salt intake did not occur in salt-sensitive young adults, and this may be linked with a hereditary predisposition to hypertension.

Adult↗

Angiotensin II blunts, while an angiotensin-converting enzyme inhibitor augments, reflex sympathetic inhibition in humans.

1. The role of angiotensin (Ang)II in and the effects of angiotensin-converting enzyme (ACE) inhibitors on the regulation of sympathetic neural activity were examined in humans. 2. We measured baseline values of muscle sympathetic nerve activity (MSNA) and its reflex inhibition in 28 patients with essential hypertension with elevated plasma renin activity (PRA; > 1.0 ng/mL per h = 0.28 ng/L per s) before and after either acute or chronic oral administration of an ACE inhibitor or placebo and in 20 normotensive subjects before and after infusion of either AngII (5 ng/kg per min = 4.8 pmol/kg per min) or vehicle (5% dextrose). Muscle sympathetic nerve activity was recorded from the tibial nerve and its reflex inhibition was evaluated during pressor responses to bolus injection of phenylephrine (2 micrograms/kg, i.v.). 3. Blood pressure was significantly decreased (P < 0.01) after the acute oral administration of captopril (25 mg), accompanied by a slight increase in MSNA in patients with essential hypertension compared with control patients who received placebo administration. Reflex changes in MSNA were significantly augmented after oral administration of captopril (-4.1 +/- 0.5 vs -6.2 +/- 0.6%/mmHg, respectively; P < 0.01), with a significant reduction of plasma AngII, while they were not affected by placebo administration. 4. In contrast, acute AngII infusion was accompanied by decreases in both PRA and MSNA in normotensive subjects. Reflex changes in MSNA were significantly reduced after AngII infusion (-11.0 +/- 0.8 vs -7.4 +/- 1.0%/mmHg, respectively; P < 0.01) but not after vehicle alone. 5. Chronic ACE inhibition by 12 week oral imidapril administration (5-10 mg/day) significantly (P < 0.05) decreased baseline values of MSNA, which were accompanied by a significant (P < 0.05) increase in the reflex inhibition of MSNA, while plasma concentrations of noradrenaline were unaffected. 6. These results indicate that AngII blunts reflex inhibition of sympathetic neural activity and that inhibition of the renin-angiotensin system by an ACE inhibitor augments reflex regulation of sympathetic neural activity and reduces baseline values in patients with essential hypertension.

Adult↗

Relation between body fat-corrected ECG voltage and ambulatory blood pressure in patients with essential hypertension.

Because adipose tissue has high electric resistance, the amount of body fat influences ECG voltage. In this study, body fat weight of patients with essential hypertension was measured by means of the impedance method and was used to correct mean ECG voltage. Then the relation between body fat-corrected mean ECG voltage (Vfm) and ambulatory blood pressure (BP) was investigated. The subjects were 172 patients with essential hypertension (88 men, 84 women, none receiving medication) between the ages of 30 and 75 years. Ambulatory BP was measured by a multi-biomedical recorder. Minimum sleep-time BP (base BP) was calculated to correspond with minimum sleep-time heart rate. The tetrapolar bioelectric impedance method was used to measure body fat (kg). Left ventricular mass (LVM) was obtained by echocardiography. Then comparisons were made with standard 12-lead ECG, and the statistical mean ECG voltage (Vm) and Vfm were derived by multivariate statistical analysis. The following formula was devised to obtain Vfm resulting from the multivariate analysis that demonstrated a high correlation with LVM (r=0.85): Vfm=0.175(Body Fat)1/3xVm+0.5 (mV). The coefficient of correlation (r) between Vfm and ambulatory BP was not smaller than that between LVM and ambulatory BP. Base systolic BP demonstrated a significantly higher r value (r=0.83) with Vfm/BSA1/2 (where BSA is body surface area) than mean daytime SBP (r=0.65). In many subjects with white-coat hypertension, Vfm/BSA1/2 was <1.33 mV/m (34 of 38 cases; sensitivity, 89%; specificity, 89%). These results indicate that Vfm is a better indicator of hypertensive left ventricular hypertrophy and that it may be useful in estimating minimum sleep-time systolic BP and in diagnosing white-coat hypertension in the outpatient clinic.

Adipose Tissue↗

Comparison of atrial natriuretic peptide versus nitroglycerin for reducing blood pressure in acute myocardial infarction.

In 10 patients with uncomplicated anterior acute myocardial infarction, within 24 hours after onset, heart rate, plasma renin activity, and the low- to high-frequency power ratio increased and high-frequency power decreased during nitroglycerin infusion; however, both heart rate and plasma renin activity did not change, the low- to high-frequency power ratio decreased, and high-frequency power increased during atrial natriuretic peptide infusion. Atrial natriuretic peptide seems to be more beneficial in its effect on autonomic nervous activity, plasma renin activity, and myocardial oxygen consumption than nitroglycerin for the treatment of anterior acute myocardial infarction.

Aged↗

Circadian variation of urinary microalbumin excretion and ambulatory blood pressure in patients with essential hypertension.

OBJECTIVE: To investigate the relationship between circadian changes in urinary microalbumin excretion (UAE), blood pressure (BP) and physical activity in patients with essential hypertension. DESIGN AND METHODS: The subjects were 45 patients with essential hypertension (EH group: 26 male and 19 female, age 56+/-12 years (mean +/- SD)) and 25 patients with diabetes mellitus (DM group: 14 male and 11 female, age 61+/-10 years). Their BP and physical activity (acceleration) were measured at 30-min intervals for 24 h by means of a multi-biomedical recorder (TM2425). Urine samples were collected during each of four 4-h daytime periods and one 8-h night-time period. From these samples, per-h UAE (UAE/h) was measured. Mean values for mean blood pressure (MBP) and acceleration were calculated for corresponding time periods. Plasma hormones were measured during an early morning rest period. RESULTS: In the EH group, a significant positive correlation was observed between circadian variation of UAE/h and MBP in 35 (78%) subjects, and the mean coefficient of correlation (r) was 0.86+/-0.12. A significant positive correlation was observed between circadian variation of UAE/h and mean acceleration value (Gh) in 25 (56%) subjects, and the mean r value was 0.70+/-0.26. Multivariate linear regression analysis showed that MBP exerted a greater influence on UAE/h than Gh. Significant positive correlations were observed between UAE/day and plasma human atrial natriuretic peptide and plasma aldosterone concentration (r = 0.50, P < 0.01; r = 0.36, P< 0.05). None of these relations, however, was observed in the DM group. CONCLUSIONS: In patients with essential hypertension, circadian changes in activity and variation of BP influence UAE/h, but no definite relationship of this kind was observed in patients with diabetes mellitus. Measurement of circadian changes in UAE or UAE/day may be useful in estimating the degree of daily stress in non-diabetic patients with essential hypertension.

Adult↗

Statistical base value of 24-hour blood pressure distribution in patients with essential hypertension.

The purpose of this study was to calculate statistically the minimum (base) blood pressure (BP) of nighttime (sleep-time) BP values obtained by ambulatory BP monitoring (ABPM) and to investigate its clinical significance. Twenty-four-hour recording of ECG with ABPM was performed directly (n=89) or indirectly (n=117) in 206 patients with essential hypertension. A telemeter was used for the direct method and a multi-biomedical recorder (TM2425) was used for indirect measurement. First, minimum heart rate (HR0=60/RR0) was determined from sleep-time ECG. The mean product of sleep-time diastolic BP (DBP) and pulse interval (RR) was divided by RR0 to obtain DBP0 [DBP0=(DBPxRR)s/RR0]. The correlation between systolic BP (SBP) and DBP was used to determine SBP0 corresponding to DBP0. Statistical base mean BP (MBP0) was calculated from these values, and its reproducibility and relation to hypertension severity were investigated. MBP0 values were similar to true base values of sleep-time MBP obtained by the direct method (mean+/-SD difference, 2.0+/-4.2 mm Hg). Direct MBP0 criteria predicted hypertension severity (mild, moderate, or severe target organ damage) more accurately (predictive accuracy, 89%) than daytime MBP criteria (53%, P<0.01). Almost the same results were obtained using indirect MBP0 criteria. Day-to-day indirect MBP0 variation (mean absolute difference) was smaller (2.4+/-1.8 mm Hg) than day-to-day daytime and nighttime MBP variation (6.3+/-5.3 and 5.4+/-3.4 mm Hg, respectively; n=61, P<0.01), and the correlation coefficient between day-to-day variations of daytime MBP and physical activity (measured by an acceleration sensor) was 0.38 (P<0.05). In conclusion, statistical base BP was almost equal to true base (minimum) BP of sleep-time BP distribution. It was closely related to the severity of hypertensive organ damage, was highly reproducible, and is considered likely to serve stochastically and physiologically as a representative BP value in an individual subject.

Adult↗

A new photo-oscillometric method employing the delta-algorithm for accurate blood pressure measurement.

OBJECTIVE: To measure blood pressure accurately, by developing a new algorithm and an indirect method employing a non-elastic cuff with a photosensor. DESIGN AND METHODS: A non-elastic cuff was wrapped around the brachium. A reflecting plate (10 mm x 40 mm) was sited on the inner central part of the cuff on the arterial side. On the opposite side of the cuff, a photosensor consisting of light-emitting and light-receiving elements was positioned. Oscillation due to arterial pulsation was measured photologically during cuff inflation. Cessation of oscillation was taken as the systolic blood pressure (SBP) and, when the delay time between photo-oscillation and cuff-pressure oscillation upstrokes was at its minimum, the transition from rapid to more stable changes in photo-oscillation was taken as the diastolic blood pressure (DBP; the delta-algorithm). We compared the blood pressures measured directly in the brachial artery with those obtained by this method and by the conventional auscultatory method in 10 normotensive and 26 hypertensive subjects [12 women and 24 men, mean age 45 +/- 16 years (mean +/- SD), with mean brachial circumference 27 +/- 2.6 cm]. The blood pressure of each subject was measured simultaneously by the direct and indirect methods five times. RESULTS: Errors (differences from direct blood pressure measurements) produced with this new method [SBP -0.8 +/- 3.1 mmHg, (mean +/- SD) DBP 0.6 +/- 2.8 mmHg] were significantly smaller than errors obtained by use of the auscultatory method (SBP -7.4 +/- 5.6 mmHg, DBP 3.0 +/- 7.1 mmHg; P < 0.001, n = 180). The delta-algorithm was easily applicable to an automatic blood pressure measuring device. CONCLUSION: This new photo-oscillometric method was more accurate than the auscultatory method for measuring blood pressure. The delta-algorithm is logical and will be useful for accurate blood pressure measurement.

Adult↗

Hemodynamic factors regulating blood pressure during sleep in patients with mild essential hypertension.

Blood pressure (BP) values (systolic BP = Ps, diastolic BP = Pd, heart rate = HR) fluctuate widely throughout the day, and are at their lowest levels during sleep (sleep-Ps = PS0, sleep-Pd = Pd0, sleep-HR = HR0). We analyzed the relationships among these values using the Windkessel model (logarithmic gradient of diastolic pressure decay A = E/R, E = elastic modulus, R = vascular resistance). Intra-arterial BP and ECG were recorded throughout 24 hours in 23 patients with mild essential hypertension (EH) by telemetry, and EEG was monitored during the night. The waveform of each BP pulse was analyzed by computer. The dye-function method was used to obtain the cardiac output while the subjects were awake, recumbent and during slow-wave sleep on the EEG. A high correlation coefficient (r) was observed between mean BP and square root of E x square root of R during sleep (r = 0.88, p < 0.001). Sleep-HR was determined from the waveform that most effectively permitted peripheral blood flow. Furthermore, the simple algebraic relationships Pd not equal to phi x Pd0 and phi not equal to FI + a1(BI) + b1 (a1, b1 = constant) were observed between Pd0 and different 24 h Pd values [FI = eA(RR0-RR); BI = baroreflex index = RR x Pd(RR0 x Pd0)-1, which was significantly correlated with the baroreflex sensitivity, r = 0.79; RR0 and RR are the RR intervals in Pd0 and Pd waves]. The mean r between Pd0 x phi and the actual Pd over 24 h was 0.91 +/- 0.02 (SD). We conclude that sleep-BP and sleep-HR depend mainly on square root of E x square root of R, m [m = log(e)(Ps/Pd)] and E/R, whereas BP variability (phi) over a 24 h period is related to HR variation, the baroreflex index and E/R in mild EH patients.

Adult↗

Doxazosin suppresses the morning increase in blood pressure and sympathetic nervous activity in patients with essential hypertension.

To investigate the effects of doxazosin on blood pressure and sympathetic nervous activity, we analyzed the circadian variation of blood pressure and the power spectrum of R-R intervals using an ambulatory multibiomedical monitoring system (TM2425) in 10 untreated outpatients with essential hypertension. After a 2-wk placebo period (P-period), we administered 1 to 4 mg of doxazosin mesilate to the patients for 2 to 6 wk (T-period). We measured systolic and diastolic blood pressure (SBP, DBP), heart rate, R-R intervals, posture, and activity with the use of TM2425. Power spectral analysis of R-R intervals was used to calculate the ratio of low to high frequency components (LF/HF). The values were compared between the P-period and T-period. Although daytime blood pressure significantly decreased during the T-period (SBP, 148.1 +/- 5.9 vs. 130.3 +/- 4.4 mmHg; DBP, 92.3 +/- 3.2 vs. 83.6 +/- 2.6 mmHg, p < 0.01), nighttime DBP did not. The LF/HF of R-R intervals in the daytime (5.8 +/- 2.0 vs. 4.9 +/- 1.2, p < 0.01) and the morning rise in blood pressure also decreased significantly (SBP, 17.5 +/- 9.4 vs. 12.1 +/- 6.5 mmHg; DBP, 12.5 +/- 6.5 vs. 8.3 +/- 5.3 mmHg, p < 0.05). We conclude that doxazosin may suppress the morning rise in blood pressure in association with a decrease in sympathetic nervous activity.

Adult↗

Circadian variation of hemodynamics and baroreflex functions in patients with essential hypertension.

It is well known that cardiovascular accidents such as myocardial infarction frequently occur in the morning, but their triggering mechanisms are not clear. The present study investigated circadian variations of hemodynamics and baroreflex functions. Twenty-three patients with essential hypertension were studied. Direct blood pressure (BP) and ECG were recorded by telemeter over 24 h, and then computer-analyzed. The pulse-contour method was used to measure cardiac output (CO) and total peripheral vascular resistance (TPR). The ratio of low to high frequency components (LF/HF) of the RR-interval on ECG was calculated by power spectral analysis. The baroreflex sensitivity index (BRI) was measured on the basis of the ratio delta RR/delta Ps (delta Ps = spontaneous decrease in systolic BP, delta RR = change in RR). Furthermore, 24-h BP changes were transformed algebraically into positive load component (PC) and negative load component (NC) by using a Windkessel model. The circadian variation of hematocrit (Ht) was also measured. The least squares method was used to determine the time at which the maximum and minimum value of each measurement occurred. Whereas the maximum values for BP and CO occurred in the evening (18:30, 17:00), the maximum values for TPR and LF/HF occurred between 06:30 and 08:00, and the minimum value for BRI occurred at 08:00. PC significantly correlated with Ps, heart rate, and CO (r = 0.81, 0.92, 0.67), and NC significantly correlated with BRI and LF/HF (r = 0.71, 0.64). PC (related to cardiovascular function) reached a maximum and NC (related to baroreflex function) reached a minimum in the late morning (11:00). Ht was highest immediately after the subjects got out of bed. These hemodynamic imbalances may negatively influence coronary blood flow in the morning.

Adult↗

Effects of insufficient sleep on blood pressure monitored by a new multibiomedical recorder.

Blood pressure varies in relation to factors such as physical activity, body position, ambient temperature, and autonomic nervous system activity. Therefore, we have developed a portable multibiomedical (PMB) recorder that monitors five parameters: indirect blood pressure, physical activity, body position, ambient temperature, and RR interval of the electrocardiogram. In the present study, we applied the PMB recorder over a 24-hour period to study the effect of insufficient sleep on blood pressure in subjects doing extensive overtime work. The parameters listed above were measured by the PMB recorder throughout a normal workday (mean period of sleep, 8 hours) and throughout a day with insufficient sleep (mean period of sleep, 3.6 hours) in 18 male technical workers aged 23 to 48 years old. Blood pressure (mean systolic/diastolic pressure +/- SD) significantly increased the day after a sleep-insufficient night (129 +/- 8/79 +/- 6 mm Hg) compared with the day after a normal night (123 +/- 8/76 +/- 7 mm Hg, P<.05). However, ambient temperature, mean number of steps per minute, and percentage of time spent in a standing position showed no significant difference between these days. Spectral analysis of RR intervals showed that the ratio of the low-frequency component on the RR power spectrum (0.05 to 0.15 Hz) to the high-frequency component (0.15 to 0.40 Hz) was higher on the sleep-insufficient day (2.17 +/- 0.37 versus 1.81 +/- 0.37), as was the urinary excretion of norepinephrine (P<.05). Heart rate was significantly higher on the sleep-insufficient day (81 +/- ll versus 76 +/- 8 beats per minute), after the data of two subjects with abnormal levels of physical activity were excluded (P<.Ol). These data suggest that lack of sleep may increase sympathetic nervous system activity on the following day, leading to increased blood pressure. The PMB recorder was useful for precisely evaluating the relationship between blood pressure and environmental factors.

Adult↗

Circadian variation in baroreflex sensitivity evaluated by beat-to-beat hemodynamic change in patients with essential hypertension.

The mechanisms underlying the higher incidence of cardiovascular events in the morning were investigated by studying the circadian variation in hemodynamics and baroreflex sensitivity (BRS) in 20 untreated inpatients with essential hypertension. Direct blood pressure (BP) and heart rate (HR) were recorded using telemetry. Cardiac output (CO) was measured by the dye dilution method. Beat-to-beat stroke volume (SV) and total peripheral vascular resistance (TPR) were obtained using the pulse contour method. The coefficient of regression between HR and systolic BP (SBP) change (delta HR/delta SBP = Ahr) was calculated for in 5 consecutive heart beats during which BP decreased spontaneously and linearly (r > 0.9). Similarly, the delta SV/delta SBP (= Asv) and delta TPR/delta SBP (= Atpr) were also measured, and the negative values of these coefficients (-Ahr, -Asv and -Atpr) were calculated. Comparisons between morning (6-11 a.m.) and evening (4-9 p.m.) values showed no significant difference in mean BP (122 vs 127 mmHg) and HR (72 vs 73 bpm). However, CO (3.7 vs 4.2 l/min), -Ahr (0.28 vs 0.43 bpm/mmHg) and -Asv (-1.5 vs 1.4 ml/mmHg) were lower in the morning than in the evening (p < 0.01). In contrast, TPR (40 vs 34 mmHg/l/min) and -Atpr (1.2 vs -1.4 min/l) were higher in the morning than in the evening (p < 0.01). These findings suggest that lower -Ahr and -Asv and higher TPR and -Atpr may cause stress to the cardiovascular system in the morning in patients with essential hypertension.

Adult↗

Role of cyclic GMP in inhibitory effects of CD-349 in isolated blood vessels.

1. We investigated the effects of CD-349, a dihydropyridine derivative with nitrate ester, on contractile responses induced by high K+, norepinephrine (NE) and Ca2+ in isolated rabbit aorta. 2. CD-349 (10(-9)-10(-5) M) and nifedipine (10(-9)-10(-5) M) equally inhibited the 64 mM KCl-induced contraction of the aortic strips in a concentration-dependent manner. 8-Br-cyclic GMP (10(-3) M) did not inhibit the KCl-induced contraction of the aortic strips. 3. CD-349 (10(-8)-10(-5) M) and 8-Br-cyclic GMP (10(-6)-10(-3) M) inhibited the 10(-6) M NE-induced contraction of the aortic strips in a concentration-dependent manner. However, nifedipine had no effect on the NE-induced contraction in rabbit aorta. 4. The inhibitory effects of CD-349 on NE-induced contraction were antagonized by treatment with methylene blue and oxyhemoglobin, while they were augmented by treatment with zaprinast. 5. CD-349 (10(-8)-10(-5) M) and 8-Br-cyclic GMP (10(-5)-10(-4) M) inhibited the NE-induced phasic contraction and Ca(2+)-induced contraction of the aortic strips preincubated with NE in Ca(2+)-free medium. However, nifedipine (10(-5) M) had little or no effect on both NE-induced phasic contraction and Ca(2+)-induced contraction of the aortic strips preincubated with NE in Ca(2+)-free medium. 6. CD-349 (10(-7)-10(-5) M) increased the levels of cyclic GMP in rabbit aorta. 7. These results indicate that CD-349 has a hybrid property deriving from Ca(2+)-antagonist and cyclic GMP increasing agents.

8-Bromo Cyclic Adenosine Monophosphate↗