Increased amplitude of the circadian variations in locomotor activity, systolic arterial pressure, and heart rate in congenic rats derived from SHRSP rats.

The circadian variations in the hemodynamics and locomotor activity (ACT) of congenic rats derived from stroke-prone spontaneously hypertensive (SHRSP) rats and Wistar-Kyoto (WKY) rats have not been studied in detail. We used radio telemetry and the maximum entropy method to examine these variations. The systolic arterial pressure of the congenic rats was intermediate between those of the SHRSP rats and WKY rats, while their heart rate was lower than that of the SHRSP rats. The congenic rats also showed the highest ACT. The circadian variations in the heart rates of the congenic rats were more like those of the WKY rats, and the variations in their ACT were more similar to those of the SHRSP rats.

Short and long term analysis of heart rate variations in spontaneously hypertensive rats: effects of DSP-4 administration.

The purpose of this study was to investigate whether or not central noradrenergic neurons were involved in the time structure of circadian variation of heart rate (HR) in hypertension. We used spontaneously hypertensive rats (SHR(Izm)) and normotensive controls (Wistar Kyoto rats, WKY(Izm)). We selectively destroyed the noradrenergic neurons in the central nervous system (CNS) by administering noradrenergic neurotoxin, N-(2-chloroethy)-N-ethyl-2-bromobenzylamine (DSP4). Frequency domain measures of variation of HR (VHR) were obtained using the maximum entropy method. The 24-h time frame in VHR is usually dominant in both SHR(Izm) and WKY(Izm). Fourteen days after the administering of DSP4, the mean 24-h systolic arterial pressure (SAP) remained higher in SHR(Izm) than in WKY(Izm). After chemical lesion, ultradian rhythms (12-, 8-, 6-, and 4-h periods) in VHR became more remarkable in both SHR(Izm) and WKY(Izm) than before chemical lesion. Before chemical lesion, an inverse relationship existed between frequency and power spectral density in VHR, demonstrating 1/f(beta) characteristics. The slope of 1/f(beta) in VHR did not differ between SHR(Izm) and WKY(Izm). After the chemical lesion it did not also differ from that of each strain in control period (before lesion). Therefore, the noradrenergic neurons may not affect the time structure of HR in SHR(Izm) and WKY(Izm) for short-term time analysis. However, the intact noradrenergic neurons in CNS may be important to keep normal cardiac autonomic function in SHR(Izm) for long-term analysis.

24-hour blood pressure in Uygur, Kazakh and Han elderly subjects in China.

The Uygur in Hotan (Xinjiang, China) are reported to have a long life expectancy. The purpose of this study was to clarify the relationship between variations in blood pressure (BP) and longevity. Cross-sectional surveillance was carried out in both Hotan and Barkol. The subjects were divided into five groups: 1. Uygur longevity subjects in Hotan (103 subjects, age >90 yr); 2. Uygur elderly subjects in Hotan (107 subjects, age 65-70 yr); 3. Han elderly subjects in Hotan (41 subjects, age 65-70 yr); 4. Kazakh elderly subjects in Barkol (117 subjects, age 65-70 yr); 5. Han elderly subjects in Barkol (50 subjects, age 65-70 yr). BP was monitored and analyzed using the fourteen devices of ambulatory BP monitoring. The prevalence of hypertension was lowest in the Uygur (16.2% in Uygur elderly subjects in Hotan; 23.7% in Uygur longevity subjects in Hotan; 27.0% in Han elderly subjects in Hotan; 42.0% in Han elderly subjects in Barkol; 50.0% in Kazakh elderly subjects in Barkol). The ratio of dips in BP was largest in the Han (57% in Han elderly subjects in Barkol; 50% in Han elderly subjects in Hotan; 50% in Uygur longevity subjects in Hotan, 49% in Uygur elderly subjects in Hotan; 17% in Kazakh elderly subjects in Barkol). The 24-h mean systolic BP in Uygur longevity subjects in Hotan was not different from those in Uygur elderly subjects and Han elderly subjects in Hotan, nor did the 24-h mean diastolic BP differ from those in Uygur elderly subjects and Han elderly subjects in Hotan respectively. In conclusion, Uygur subjects seem to be less hypertensive, compared to Kazakh subjects. Uygur longevity subjects had more dipping in their BP variation than did the Kazakh subjects in Xinjiang, China.

Heart rate responses to altered ambient oxygen in early (days 3-9) chick embryos in the intact egg.

Normal heart rate (HR), and the HR responses to hypoxia and hyperoxia during early heart development in chick embyros have not been studied in detail, particularly in undisturbed embryos within the intact egg. HR was measured in day 3-9 chick embryos at 38 degrees C using relatively noninvasive impedance cardiography. Embryos were exposed to air (control) and to hypoxic (10% O2) or hyperoxic (100% O2) gas for a 2-h or 4-h period, during which HR was continually monitored. Control (normoxic) HR increased from about 150 beats per min (bpm) on day 3 to about 240 bpm on days 7-9. HR in very early embryos showed a variety of moderate responses to hypoxia (all survived), but as development progressed beyond day 6, hypoxic exposure induced a profound bradycardia that frequently terminated in death before the end of the measurement period. In contrast to the marked developmental changes in hypoxic sensitivity, HR showed little response to hyperoxia throughout development, suggesting no "hypoxic drive" to HR. We speculate that hypoxia has little effect early in development because of the embryo's small absolute O2 demand, but as the embryo grows, hypoxia represents a progressively more severe perturbation. Although general trends were identified, there was considerable variation in both HR and HR responses to ambient O2 changes between individuals of the same developmental stage.

Cardiac rhythms in chick embryos during hatching.

Avian embryos develop within a hard eggshell which permits the measurement of heart rate while maintaining an adequate gas exchange through the chorioallantoic membrane. Heart rate has been determined from cardiogenic signals detected either noninvasively, semi-invasively or invasively with various transducers. Firstly, we reviewed these previously-developed methods and experimental results on heart rate fluctuations in prenatal embryos. Secondly, we presented new findings on the development of heart rate fluctuations during the last stages of incubation, with emphasis on the perinatal period, which remained to be studied. Three patterns of acceleration of the instantaneous heart rate were unique to the external pipping period: irregular intermittent large accelerations, short-term repeated large accelerations and relatively long-lasting cyclic small accelerations. Besides these acceleration patterns, respiratory arrhythmia, which comprimised oscillating patterns with a period of 1-1.5 s, appeared during the external pipping period. Furthermore, additional oscillating patterns with a period of 10-15 min were found in some externally pipped embryos.

Calcium channel blockers shorten the periodicity of ultradian variation in blood pressure in patients with essential hypertension.

We studied ultradian and circadian variations in blood pressure (BP) in patients with essential hypertension who were receiving antihypertensive agents. No patient had previously received antihypertensive agents before this study began. After a 2-wk control period, we performed ambulatory blood pressure monitoring (ABPM) in 86 patients with essential hypertension (WHO stages I or II). The patients were then given a long-acting angiotensin converting enzyme inhibitor (ACEI) (captopril or imidapril), a beta-receptor blocker (arotinolol or bisoprolol), or a calcium channel blocker (nisoldipine or benidipine) twice daily to control BP. We evaluated the patients' BP once every 2 wk to ensure optimal control. After 12 wk, ultradian and circadian variations in BP were analyzed by the maximum entropy method (MEM). All antihypertensive agents decreased office systolic BP (SBP), office diastolic BP (DBP), 24-h SBP, and 24-h DBP. ACEI did not change office, 24-h, daytime, or nighttime pulse rate (PR). Arotinolol and bisoprolol decreased 24-h PR. All antihypertensive agents decreased 24-h, daytime, and nighttime pressure rate product. MEM showed that no antihypertensive agent affected the circadian variation in the 1st peak (24-h periodicity) of SBP, DBP, or PR. However, calcium channel blockers shortened the periodicity of circadian variations in the 2nd peak (12-h periodicity) of SBP and the 3rd peak (8 to 6 h periodicity) of SBP. Therefore, ultradian variations in BP should be carefully monitored in hypertensive patients treated with calcium channel blockers.

[Clinical effects of beni-koji in mild essential hypertension--a multi-center double-blind comparison with placebo].

Antihypertensive effects of beni-koji were studied using 29 outpatients with mild hypertension in a placebo-controlled double-blind comparative fashion. After a 4-week vehicle (apple juice) run-in period, 13 patients were assigned to receive beni-koji aqueous extracts containing juice once daily (27 g of beni-koji eq. per day) for 8 weeks and 16 were assigned to vehicle. Two patients assigned to the vehicle group did not complete the study. In addition to casual blood pressure, 24-hr non-invasive ambulatory blood pressure (ABP) was monitored in 6 patients given the beni-koji drink and 5 patients given the vehicle. 1) In the beni-koji group, both casual systolic and diastolic pressure decreased significantly during the treatment period (from 150 +/- 10/96 +/- 6 mmHg to 140 +/- 10/89 +/- 10 mmHg, p < 0.01). The averages of the 24-hr blood pressure recorded in ABP (24-BP) also significantly decreased (from 141 +/- 17/95 +/- 13 mmHg to 132 +/- 21/86 +/- 10 mmHg, p < 0.05) when compared with those of the control period. Casual pressure normalized (less than 140/90 mmHg) in 4 patients who received beni-koji. Circadian variation of the blood pressure by ABP showed a significant decrease during the daytime. 2) In the vehicle group, casual systolic pressure did not change significantly (from 155 +/- 8 mmHg to 151 +/- 12 mmHg), but diastolic pressure decreased significantly (98 +/- 7 mmHg to 93 +/- 6 mmHg). Casual blood pressure did not normalize in any of the patients and 24-BP did not change significantly. 3) Summative evaluation of safety showed that no problems appeared in the beni-koji group. In conclusion, beni-koji appears to be an effective and safe food material for mild essential hypertension. The mechanism of the antihypertensive effect of beni-koji still remains to be investigated.

[Effect of calcium antagonist (benidipine) and alpha 1 blocker (urapidil) on renal hemodynamic responses to two acute environmental stresses in spontaneously hypertensive rats (SHR)].

Renal hemodynamic responses were studied in spontaneously hypertensive rats (SHR) and Wistar-Kyoto Rats (WKY) to two acute stresses: environmental stress (foot shock (FS) and air jet (AS)). The effects of calcium channel blocker (benidipine) and alpha 1 blocker (urapidil) on these responses were studied using an ultrasonic pulsed Doppler flowmeter. The increments in mean arterial pressure (MAP) and renal vascular resistance (RVR) were greater in SHR during both stresses. On the other hand, the decrease in the renal blood flow (RBF) with these stresses almost disappeared with renal denervation. These renal hemodynamic responses in SHR disappeared with alpha 1 blocker (urapidil), but not with calcium channel blocker (benidipine). The sympathetic nervous system became hyperactive in SHR under environmental stress, Which induced specific renal hemodynamic change. These results suggest that investigations on essential hypertension should focus on clarifying not only systemic hypertensive reaction, but also changes in renal hemodynamics. Furthermore, it is necessary for antihypertensive therapy to take these hemodynamic changes into consideration.

Altered basal firing pattern and postactivation inhibition of locus coeruleus neurons in spontaneously hypertensive rats.

We compared the spontaneous unit activity and inhibition of impulse activity following antidromic activation (postactivation inhibition, PAI) of locus coeruleus (LC) neurons in spontaneously hypertensive rats (SHR) with those of LC neurons in Wistar-Kyoto rats (WKY). Spontaneous spikes of the LC were analyzed by interspike time histograms. The basal unit activity and variation coefficient of the interspike interval were decreased in SHR. The duration of the PAI which was yielded by antidromic activation from the dorsal noradrenergic bundle was shortened in SHR. These findings suggest that SHR LC neurons possess an altered basal firing pattern and inhibitory mechanism.

The effect of manidipine on renal hemodynamics in essential hypertensive patients: responses to acute stress.

The effects of the calcium antagonist manidipine 20 mg/day on changes in blood pressure and renal hemodynamics in response to acute stress by the mental arithmetic test (MAT) and the cold pressor test (CPT) were investigated in 14 patients with essential hypertension (median age: 50 +/- 2, WHO stage I-II). During the drug-free period, acute stress by both MAT and CPT caused an increase in the renal vascular resistance index (RVRI) [% change in RVRI, 17% for MAT (p < 0.05) and 26% for CPT (p < 0.01)] and an increase in blood pressure [% change in mean blood pressure (MBP): 17% for MAT (p < 0.001) and 16% for CPT (p < 0.001)]. CPT stress resulted in a reduction in RAFV (% change in RAFV: -12%, p < 0.05). Oral administration of manidipine resulted in hypotensive effects at rest [MBP: from 116 to 99 mmHg, p < 0.001], no change in RAFV (31.3 to 32.9 cm/sec, p = ns), and reduced RVRI (from 3.9 to 3.2 mmHg.sec/cm, p < 0.02). Manidipine inhibited the hypertensive response to acute stress by both MAT and CPT [% change in MBP: from 17% to 11% for MAT (p < 0.02) and from 16% to 11% for CPT (p < 0.01)] and also inhibited the increase in RVRI [% change in RVRI: from 17% to -1% for MAT (p < 0.05) and from 26% to 8% for CPT (p < 0.01)]. Manidipine has beneficial effects on blood pressure and renal hemodynamics at rest in patients with essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary sodium concentration modifies catecholamine release with stress in spontaneously hypertensive rats.

A high sodium diet increased the plasma norepinephrine (PNE) only in resting spontaneously hypertensive rats (SHR). SHR on either a high or low sodium diet showed a greater increase in arterial pressure (AP) than Wistar-Kyoto rats (WKY) with foot shock (FS). However, neither a high nor low sodium diet enhanced the increment of AP in both SHR and WKY with FS. Only a low sodium diet enhanced the increment of PNE and plasma epinephrine in SHR with FS. Extreme restriction of sodium intake might thus enhance the response of sympathetic activation with stressful stimuli.

Diminished sympathetic excitation of locus coeruleus noradrenergic neurons in the conscious mature spontaneously hypertensive rat.

We undertook a study to determine whether the activation of the nucleus locus coeruleus might be responsible for the sympathetic hyperactivity in the spontaneously hypertensive rat (SHR). Conscious mature SHR showed increased arterial pressure and plasma catecholamines with electrical stimulation of the locus coeruleus. However, SHR showed smaller increases in arterial pressure and plasma noradrenaline than Wistar-Kyoto rats (WKY). The spontaneous unit discharge in locus coeruleus neurons responded reciprocally to peripherally induced changes in arterial pressure and blood volume. However, the unit discharge in the SHR locus coeruleus is less responsive than that in WKY. Therefore, the locus coeruleus in mature SHR does not seem to be involved in the hyperactivity of the sympathetic nervous system. However, this may not be the case in young SHR.