Motofumi Maguchi

Autonomic Nervous Function in Non-dipper Essential Hypertensive Subjects: Evaluation by Power Spectral Analysis of Heart Rate Variability

Autonomic nervous function was evaluated by means of power spectral analysis of heart rate variability in hospitalized dipper (n = 31) and non-dipper (n = 31) essential hypertensive subjects. Twenty-four-hour blood pressure (BP) measurement was performed by the cuff-oscillometric method to evaluate the nocturnal decrease of BP. The non-dipper subjects were defined as those whose nocturnal decrease of systolic BP was < 10% of daytime BP. Power spectral analysis of RR interval was performed from Holter ECG every 10 minutes by the maximum entropy method to obtain the low-frequency band (LFB, 0.04 to 0.15 Hz), which is an index of both parasympathetic and sympathetic nervous activities, and the high frequency band (HFB, 0.15 to 0.4 Hz), which reflects parasympathetic nervous activity. LFB and HFB were averaged every hour to obtain hourly LFB and HFB values. Total LFB and total HFB were calculated as the mean values of 24 hourly averaged LFBs and HFBs. Both LFB and HFB were significantly lower in non-dipper hypertensives than in dipper subjects throughout the day. In dipper hypertensives, LFB showed a nocturnal decrease, whereas HFB was significantly increased during the nighttime. However, these diurnal changes in LFB and HFB were significantly blunted in non-dipper subjects. These findings indicate that non-dipper hypertensive subjects were characterized with a decreased physiological circadian fluctuation on autonomic functions compared with dipper subjects. This alteration in the autonomic nervous function may explain the non-dipper phenomenon in essential hypertension.

Platelet-derived growth factor induces apoptosis in vascular smooth muscle cells: roles of the Bcl-2 family

Apoptosis (programmed cell death) is observed in vascular smooth muscle cells (VSMC) in atherosclerotic lesions and stenotic lesions after injury, and modulates the cellularity of these lesions. It is recognized that cell growth and apoptosis are two linked processes. Platelet-derived growth factor (PDGF) induces VSMC proliferation and migration in vitro. We studied the effect of PDGF on apoptosis in VSMC. Cultured rat VSMC were treated with PDGF-AA or PDGF-BB. PDGF-BB induced cell death in cultured VSMC in a time- and dose-dependent manner, but PDGF-AA did not. Gel electrophoresis of genomic DNA and in situ DNA labeling confirmed that the cell death induced by PDGF-BB is apoptosis. PDGF-BB treatment reduced bcl-2 mRNA and bcl-xl mRNA expression, in contrast, induced bcl-xs mRNA expression, linked with the induction of apoptosis in cultured VSMC.

Autonomic Nervous Function in Essential Hypertension in the Elderly: Evaluation by Power Spectral Analysis of Heart Rate Variability

Autonomic nervous function in elderly essential hypertensive patients was investigated by power spectral analysis of heart rate variability. Fifty-seven essential hypertensive patients participated in this study. They were divided into two groups: the middle-aged group (age < or = 59 years, n = 30) and the elderly group (age > or = 60 years, n = 27). All examinations were performed during hospitalization. Power spectral analysis of R-R interval was performed from Holter electrocardiogram every 10 min by the maximum entropy method to obtain the low frequency band (LFB; 0.04 to 0.15 Hz), which is an index of both sympathetic and parasympathetic nervous activity. Twenty-four-hour blood pressure measurement was performed by the cuffoscillometric method to evaluate the nocturnal decrease in blood pressure. Nondipper patients were defined as those whose nocturnal decrease in systolic blood pressure was < 10% of daytime blood pressure. Both LFB and HFB were significantly lower in elderly hypertensive patients than in middle-aged patients (P < .001 and P < .05, respectively). Elderly nondipper patients had further reduced power spectral densities throughout the day. Both LFB and HFB showed a negative correlation with age. However, the age-related decline of power densities was more prominent in dipper patients and was not statistically significant in nondipper patients. These findings indicate that the nondipper phenomenon is superimposed on age-related attenuation of autonomic nervous function in essential hypertension.

Asymptomatic Cerebrovascular Damages in Essential Hypertension in the Elderly

To investigate the underlying mechanisms of asymptomatic cerebrovascular damage, the diurnal change in blood pressure was evaluated in hypertensive patients with silent cerebral infarction (SCI). Sixty elderly hypertensive patients (age > or = 60 years) were matched with 40 middle-aged patients (age < or = 59 years) for sex and left ventricular mass index (LVMi). Lacunar lesions were evaluated by magnetic resonance imaging as SCI. The presence and the severity of SCI increased with age. In the middle-aged group, the presence of SCI was significantly related to 24-h blood pressure and LVMi evaluated by echocardiography. In elderly patients, the presence of SCI had no relationship with 24-h blood pressure or LVMi. The lowest level of nocturnal diastolic blood pressure showed a J-shaped relationship with the incidence of SCI in the elderly patients. These findings indicate that the hemodynamic characteristics underlying the development of SCI differ between middle-aged and elderly hypertensive patients. A different approach to the treatment of hypertension in the elderly appears necessary.

Angiotensin-Converting Enzyme Gene Polymorphism in Essential Hypertensive Patients in Japanese Population

Association between angiotensin-converting enzyme (ACE) gene polymorphism and essential hypertension in a Japanese population with the same socioeconomic back ground was investigated. Insertion-deletion (I/D) polymorphism of the ACE gene located on intron 16 was detected by polymerase chain reaction. Association between ACE gene polymorphism and family history of essential hypertension as well as the development of vascular damage in eye fundi were also investigated. Variation at ACE loci did not contribute to essential hypertension and the vascular damages in eye fundi. These results suggested that the ACE gene was not directly responsible for essential hypertension in this particular Japanese population with the same socioeconomic background.

Molecular structure and function of rat platelet-derived growth factor β-receptor gene promoter

Objective To understand the regulatory mechanism of platelet-derived growth factor β-receptor gene expression. Methods A 1.7 kb genomic fragment was obtained from a rat genomic library. After we had determined an entire sequence of this fragment, transcription start sites were determined both by primer extension analysis and by riboprobe mapping. We performed a functional promoter assay by using a dual-luciferase reporter system. Progressive 5′-deletions of the fragment and site-directed mutagenesis for the CCAAT motif located at −67 or −94 were used for the assay, and their promoter activities in vascular smooth muscle cells were assessed. Gel-mobility shift analysis was also performed for the CCAAT motif at −67. Effects of the upstream sequence spanning −310 through −120 on heterologous gene promoters were also investigated. Results Multiple transcription start sites were observed in the 5′-flanking region, and the 1.7 kb sequence was actually active as a functional promoter in vascular smooth muscle cells. Two important sequences responsible for the basal transcriptonal activity were identified by the functional promoter assay. One was the CCAAT motif at −67 which acts as a promoter itself, and the other was the upstream region spanning −310 through −210 which positively regulates the basal promoter activity. Conclusion The basal promoter activity of the rat platelet-derived growth factor β-receptor gene is mainly regulated by the interaction or coordination of two sequences, the CCAAT motif and the upstream control element.

[Hepatopulmonary syndrome: clinical report of two cases].

症例1は57歳,女性.労作時呼吸困難を主訴に受診. PaO250.6Torrと低酸素血症を認めた.症例2は68歳,女性.肝細胞癌の治療目的にて入院中に労作時息切れが出現. PaO255.3Torrと低酸素血症を認めた.両症例とも基礎疾患として肝硬変症を認めること,ガス交換異常を伴う低酸素血症を認めること,マルチスライスCT (MSCT)にて肺内末梢血管拡張を認めることから肝肺症候群と診断した.

End-organ damages in essential hypertension in the elderly

To elucidate the characteristics of end-organ damage in essential hypertension in the elderly, the progression of end-organ damage, with respect to deterioration of renal function and changes in the optic fundi, were compared between young and elderly essential hypertensive patients with the same left ventricular mass index (LVMI). Forty five elderly hypertensive patients (age > or = 65 years) were matched with 40 young patients (age < or = 55 years) for sex and LVMI. All studies were performed under hospitalisation to uniform the background of diet and daily activity. Compared with young hypertensive patients, elderly patients were characterised to have advanced end-organ damage. In young patients, the levels of progression of end-organ damage were significantly correlated with each other, while in elderly patients no relation was observed. In young patients, LVMI was significantly correlated with urinary and plasma noradrenaline, PRA and 24 h blood pressure. In elderly patients, LVMI correlated only with 24 h systolic blood pressure.