Hiromi Mitsubayashi

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.

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.

Non-dipping blood pressure variations in adult Kazakhs are derived from decreased daytime physical activity and increased nighttime sympathetic activity.

Abstract Many of the elderly Kazakhs have been found to exhibit non-dipping blood pressure variations (BPV). Such variations are seen in both normotensive and hypertensive Kazakhs. The purpose of this study was (1) to determine whether middle–aged Kazakhs also include large numbers of non-dippers, (2) to compare the characteristics of non-dipping and dipping, and (3) to clarify the mechanisms responsible for non-dipping type BPV by examining the autonomic nervous activity and physical activity. We performed ambulatory blood pressure (BP) monitoring. The subjects were divided into two groups (dipping and non-dipping type). We monitored the subjects’ physical activity with accelerometry and assessed their autonomic nerve activity by performing a frequency domain analysis of their heart rate variability (HRV). The power spectral density (PSD) of the HRV was calculated using fast Fourier transformation. We analyzed the systolic blood pressure (SBP) variations with the maximum entropy method (MEM). The dippers and non-dippers accounted for 48% and 52% of the subjects, respectively. MEM analysis revealed that the SBP variations of the non-dippers exhibited a 24 hour periodicity with a very weak PSD as well as an ultradian periodicity. The non-dippers exhibited higher low-frequency/high-frequency (LF/HF) ratio and lower HF/(LF + HF) ratios than the dippers, particularly during the nighttime. In addition, the non-dippers performed less physical activity than the dippers. These differences in cardiac autonomic function and physical activity might contribute to the generation of a weak circadian rhythm in SBP, and thus, ultimately lead to the non-dipping SBP variations observed in non-dipper Kazakhs.

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.

Ps 02-59 Non-dipping-type Blood Pressure Variations In Young Kazakhs Derived From Increased Sympathetic Activity In The Morning

Objective: Many cases of non-dipping-type blood pressure variations and hypertension have been documented amongst elderly and middle-aged Kazakhs. The purpose of this study was to discover whether there are also large numbers of non-dippers among young Kazakhs and to compare the blood pressure variations seen in these individuals with those observed in age-matched dipping-type Kazakhs. Design and Method: We performed ambulatory blood pressure monitoring and defined non-dippers as individuals that exhibited a nighttime systolic blood pressure (SBP) reduction of <10% compared with their daytime SBP. There were 40 subjects, and they were divided into Kazakhs with dipping-type blood pressure variations (9–10 years old, n = 29) and Kazakhs with non-dipping-type blood pressure variations (9–10 years old, n = 11). We monitored autonomic nerve activity by measuring heart rate variability (HRV) with electrocardiography for 24 hours. We analyzed the variations in SBP with the maximum entropy method (MEM). Results: Dippers and non-dippers accounted for 73% and 27% of the subjects, respectively. The physiological characteristics of the dippers and non-dippers did not differ, nor did their 24-hr SBP values. However, daytime SBP was lower and nighttime SBP was higher in the non-dippers than the dippers (non-dippers vs. dippers: daytime SBP: 117 ± 5 vs. 123 ± 10 mmHg, P = 0.022; nighttime SBP: 109 ± 7 vs. 97 ± 7 mmHg, P = 0.005). MEM analysis of the non-dippers detected SBP variations with a 24-hr frequency periodicity, a very weak power spectral density (PSD), and an ultradian periodicity. The HRV analysis revealed that the low frequency/high frequency ratio was lower in the non-dippers than in the dippers during the morning. Conclusions: Young non-dipping Kazakhs exhibited SBP variations with a 24-hr frequency periodicity, a very weak PSD, and an ultradian periodicity. Furthermore, the non-dippers displayed less sympathetic nerve activity during the morning than the dippers.

MPS 13-05 LOCOMOTOR ACTIVITY IN CONGENIC SHRSPwch1.0 RATS IS DERIVED FROM THE INCREASE IN SYSTOLIC ARTERIAL PRESSURE BUT NOT THE SYSTOLIC ARTERIAL PRESSURE LEVEL ITSELF

Objective: Congenic rats (SHRSPwch1.0) were produced from stroke-prone SHR/Izumo rats (SHRSP/Izm) and Wistar-Kyoto rat/Izumo rats (WKY/Izm). We previously found that the systolic arterial pressure (SAP) and heart rate (HR) of the SHRSPwch1.0 were lower than those of the SHRSP/Izm. However, the SHRSPwch1.0 exhibited greater locomotor activity (ACT) than the SHRSP/Izm. The purpose of this study was to investigate the ACT characteristics of SHRSPwch1.0 in a time-series analysis. Design and Method: We used ten mature male SHRSPwch1.0 and ten male age-matched SHRSP/Izm as controls. They were kept under a 12-hour light and dark cycle in identical conditions. The rats’ SAP, HR, and ACT were monitored using radio telemetry, and their ACT was analyzed using the maximum entropy method to enable a spectral analysis of ACT. Results: All of the examined ACT values (24-hour, dark period, and light period) were greater in the SHRSPwch1.0 than in the SHRSP/Izm. A time-series analysis of ACT in the SHRSPwch1.0 revealed both circadian (23.379 hours) and ultradian variations (16.197 hours and 12.184 hours). On the other hand, the ACT of the SHRSP/Izm exhibited circadian variations (23.190 hours) and an almost imperceptible ultradian rhythm. The power spectral density of the ACT spectrum was greater in the SHRSPwch1.0 than in the SHRSP/Izm. A stronger correlation was noted between ACT and SAP in the SHRSPwch1.0 than in the SHRSP/Izm. In addition, the ACT response to increases in SAP was stronger in the SHRSPwch1.0 than in the SHRSP/Izm. However, the ACT response to increases in HR did not differ between the SHRSPwch1.0 and SHRSP/Izm. Conclusions: These findings suggest that ACT continues for longer in SHRSPwch1.0 than in SHRSP/Izm. In SHRSPwch1.0, ACT is strongly correlated with the magnitude of increases in SAP, but not the SAP level itself or the size of increases in HR.

272 HEART RATE RESPONSE DURING LOCOMOTOR ACTIVITY IS BETTER MAINTAINED IN CONGENIC RAT

Objectives, Background: The congenic rats (SHRSPwch1.0) were derived from stroke-prone SHR/Izm (SHRSP/Izm) and Wistar-Kyoto rat/Izm (WKY/Izm). We found that systolic arterial pressure (SAP) was an intermediate value between SHRSP/Izm and WKY/Izm and that the locomotor activity (ACT) was the greatest amongst these strains. To study the interrelationship amongst SAP, heart rate (HR) and ACT in SHRSPwch1.0, we evaluated the responses of SAP and HR during increased ACT in SHRSPwch1.0 and compared to those in SHRSP/Izm. Design and methods: We used ten male mature SHRSPwch1.0 and 10 age-sex matched SHRSP/Izm, and monitored SAP, HR and ACT using radio-telemetry. The responses of SAP and HR during increase ACT were calculated by (mean nighttime SAP-mean daytime SAP)/(mean nighttime ACT-mean daytime ACT) and that of HR by (mean nighttime HR-mean daytime HR)/(mean nighttime ACT-mean daytime ACT). Results: SAP in SHRSPwch1.0 was lower than in SHRSP/Izm (mean±SD, 194±9 vs. 229±15mmHg, P=0.0012). HR in SHRSPwch1.0 was slower than in SHRSP/Izm (310±9 vs. 381±45 beats/min, P=0.0110). ACT in SHRSPwch1.0 was higher than that in SHRSP/Izm (62±47vs. 26±27, median, 58 vs.18, IQR, 33 vs.18 counts/10 sec, all P<0.0010). SAP response during increased ACT in SHRSPwch1.0 did not differ from that in SHRSP/Izm. However HR response during increased ACT was greater in SHRSPwch1.0 than that in SHRSP/Izm (4.75±4.01 vs. 0.16±0.24 beats/counts/10 sec, P=0.00555). Conclusions: The HR response during increased ACT is greater in congenic rat than that in SHRSP. Therefore, the relationship between HR and ACT may better be maintained in congenic rat than that in SHRSP.

CIRCADIAN VARIATIONS IN HEMODYNAMICS AND LOCOMOTOR ACTIVITY IN CONGENIC RATS: PP.29.153

Objective: The congenic rats (SHRSPwch1.0) were derived from stroke-prone SHR/Izumo (SHRSP/Izm) and Wistar-Kyoto rat/Izumo (WKY/Izm). We studied the circadian variations of systolic arterial pressure (SAP), heart rate (HR) and locomotor activity (ACT) in SHRSPwch1.0. We also studied the effect of central selective noradrenergic neurotoxin, DSP-4 (N-2-chloroethyl-N-ethyl-2-bromobenzylamine HCl), on the circadian variations of SAP, HR and ACT. Methods: We used ten male mature SHRSPwch1.0 and ten age-sex matched SHRSP/Izm for the control. SAP, HR and ACT were monitored using radio-telemetry, and circadian variations in SAP, HR and ACT were analyzed using the maximum entropy method. Results: SHRSPwch1.0 were heavier than SHRSP/Izm (352 ± 15 vs. 279 ± 15 g, P = 0.0001). As expected, SAP in SHRSPwch1.0 was lower than in SHRSP/Izm (194 ± 9 vs. 229 ± 15mmHg, P = 0.0110). HR in SHRSPwch1.0 was slower than in SHRSP/Izm (310 ± 9 vs. 381 ± 45 beats/min, P = 0.0110). Both light period and dark period SAP and HR in SHRSPwch1.0 were lower than those in SHRSP/Izm. The circadian variations of SAP, HR and ACT in SHRSPwch1.0 were clearly evident, compared to SHRSP/Izm. 24-hr periodicities were dominant in SAP, HR and ACT of SHRSPwch1.0, compared to those in SHRSP/Izm. DSP-4 did not affect the 24-hr periodicities of SAP, HR and ACT in SHRSPwch1.0. However, it reduced the power of spectral density (PSD) of SAP in SHRSPwch1.0. Conclusions: The circadian variations of SAP, HR and ACT appear better maintained in SHRSPwch1.0, compared to SHRSP/Izm. Further work is needed to confirm the effect of noradrenergic neurons on circadian variations of SAP, HR and ACT.

ELECTROLYTES AND HEART RATE VARIABILITY AMONGST NON-DIPPER KAZAKH, XINJIANG, CHINA: PP.19.248

Objective: Large numbers of systolic blood pressure (SBP) of non-dippers and cases of hypertension have been documented amongst the Kazakh population living in Xinjiang, China. In reference to electrolytes and heart rate variability (HRV), the current study attempted to determine the mechanism responsible for such increased non-dipper numbers within this population group. Methods: We defined non-dippers as having a nocturnal SBP drop of < 10% compared to daytime SBP. Kazakhs who exhibited non-dipping were defined as non-dippers and the others as dippers. Analysis of electrolytes and HRV were performed for all enrolled Kazakhs. participants were asked to maintain daily routine activities during the ambulatory blood pressure monitoring, urine and blood sampling. Results: There were only few differences in blood pressure and pulse rate between dippers and non-dippers. Although serum creatinine in non-dippers did not differ from dippers, the urinary potassium excretion was lower in non-dippers than dippers (17.9±7.9 vs. 22.9±10.6 mEq/day, P = 0.01990). Frequencies of highest spectral densities (PSD) exhibited a periodicity of approximately 24-hr for mean SBP in the dippers. However, amongst non-dippers there was a similar 24-hr periodicity exhibiting negligible change in high PSD frequency. Compared to dippers, a lower PSD for both low frequency/high frequency [LF/HF] and high frequency/(low frequency + high frequency)[HF/(LF + HF) was observed in non-dippers. Conclusion: These alterations in potassium and cardiac autonomic function may affect the circadian rhythm, leading to non-dipping variations of SBP seen amongst this Kazakh population group.