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A questionnaire survey was administered to Japanese clinical specialists in hypertension in order to gauge their opinions on the 1999 revised version of the Guidelines for Hypertension in the Elderly prepared by the Comprehensive Research Project on Aging and Health of the Ministry of Health and Welfare. Out of 162 council members of the Japanese Society of Hypertension, 122 (75%) replied. The majority (93%) of respondents approved of the guidelines in general, and 72% of them approved of the age-related setting of a therapeutic goal for blood pressure. Sixty-five percent of respondents selected long-acting Ca antagonists, ACE inhibitors and low-dose diuretics as first-line agents for hypertension without complications in the elderly. The results of the questionnaire survey should be reflected in the next version of the guidelines. (Hypertens Res 2002; 25: 69-75)

Serial changes of left ventricular (LV) geometry and function during the development of hypertension were studied in 50 Dahl salt-resistant (DR) and 88 Dahl salt-sensitive (DS) rats fed an 8% NaCl diet beginning at the age of 6 weeks. Echocardiography at 6, 8, 11, 13, 14, 15, and 18 weeks and in vivo invasive hemodynamic determination at 6, 8, 11, 14, and 18 weeks were performed. After 11 weeks, 33 DS rats were observed for survival analysis. The survival analyses showed that the incidence of death was 57.6% due to heart failure, 27.3% due to stroke, and 15.2% due to sudden death. However, death in the early stages of hypertension was due almost entirely to sudden death or stroke. A high value of relative wall thickness (RWT) and a small end-diastolic dimension were predictive of sudden death and stroke, but LV mass (LVM) was not. Concerning the change in LV geometric patterns, LVM continued to increase to 18 weeks. The RWT increased or remained at a plateau up to 13 weeks, and then progressively decreased after 13 weeks. In contrast, LV function was hyperdynamic between 8 and 11 weeks when compared to DR rats. However, after 13 weeks, all hemodynamic variables of DS rats deteriorated progressively, and all DS rats died of heart failure. Thus, our study indicates that the cardiovascular events associated with the progression of hypertension vary widely according to the stage of hypertension and that RWT is more sensitive in predicting LV conditions than LVM in hypertension.

To elucidate the mechanism of left ventricular dysfunction associated with left ventricular hypertrophy in hypertension, coronary blood flow (CBF) and left ventricular mass (LVM) were measured in 62 patients with essential hypertension (mean age, 54±13 years) and 22 normotensive control subjects (mean age, 57 ±13 years). According to the indicator fractionation principle, CBF/cardiac output (CO), estimated on the basis of the ratio of myocardial uptake/total injected dose of thallium-201 (% cardiac uptake), was measured. CBF and CBF per 100g of myocardium (unit CBF) were calculated according to the following formulas: CBF=% cardiac uptake×CO, and unit CBF=(CBF/LVM)×100, where CO and LVM are echocardiographically determined. Midwall fractional shortening (FS) and isovolumic relaxation time (IRT) were calculated as the indices of systolic and diastolic functions. CBF was greater in hypertensives than in controls (218.2±74.0 vs. 187.4±40.4ml/min, p

Calponin has been implicated in the regulation of smooth muscle contraction. Basic calponin, one of the calponin isoforms, is expressed exclusively in smooth muscle cell (SMC)-rich tissues, and is considered to be a phenotypic marker of differentiated SMC. To define the molecular mechanism of SMC-specific gene transcription in humans, we isolated and characterized the 5′-flanking region of this gene. Sequence analysis revealed that several putative cis-acting elements were clustered within a 500-bp sequence upstream of the transcription start site. However, the 1.9-kb promoter region obtained herein lacked a completely matched consensus sequence of the CArG box that is commonly identified in the promoter region of other SMC-specific genes. A luciferase assay demonstrated that the 1.9-kb promoter region was sufficient to drive a basal transcriptional activity not only in human vascular smooth muscle cells (VSMC) but also in HeLa cells. In particular, the sequence between positions -1, 906 and -867 had a significantly higher transcriptional activity in VSMC than in HeLa cells. In contrast, the promoter activity was drastically decreased between positions -327 and -257 in both types of cells. These results indicate that the sequence spanning from position -327 to -257 contains an essential domain involved in the basal transcriptional activity of the human basic calponin gene, and that the distal region of the 1.9-kb 5′-flanking sequence presented herein may play a pivotal role in the phenotypic modulation of VSMC. (Hypertens Res 1999; 22: 187-193)

To compare the incidence of cough between two angiotensin converting enzyme (ACE) inhibitors, imidapril and enalapril, comparative crossover study was performed in 489 patients (228 men and 261 females) with essential or renal parenchymal hypertension. Patients were randomly assigned to one of two treatment groups, a group receiving imidapril for 12wk (Period I) followed by enalapril for 12wk (Period II), and a group in which the order of drugs was reversed. The occurrence of cough during treatment was monitored by questionnaire in all cases. There were no differences in background characteristics between the two groups. The incidence of cough during Period I was 15.2% (32/210) in the group initially treated with imidapril (Group IE) and 38.6% (85/220) in the group initially treated with enalapril (Group EI), the difference being statistically significant (p

This study was conducted to quantify coronary blood flow (CBF) noninvasively according to the fractionation principle and to elucidate the relation between CBF and left ventricular hypertrophy. CBF/cardiac output (CO), estimated on the basis of the ratio of myocardial uptake/total injected dose of thallium-201 (% cardiac uptake), was determined in 14 control subjects and 40 patients with essential hypertension. CBF and CBF per 100 g of myocardium (unit CBF) were calculated according to the following formulas: CBF= % cardiac uptake x CO, and unit CBF = (CBF/LVM) X 100, where CO and left ventricular mass (LVM) are echocardiographically determined. There was good reproducibility of % cardiac uptake (r = 0.983, p < 0.0001). Percent cardiac uptake was greater in hypertensive patients (4.65+/-1.44%) than in control subjects (3.64+/-0.64%), and there was a positive correlation between % cardiac uptake and LVM. CBF (ml/min) was greater in hypertensive patients (240.7+/-80.5) than in control subjects (194.9+/-36.9), but unit CBF (ml/min/100 g) was less in hypertensive patients (102.2+/-26.7) than in control subjects (150.3+/-30.5). Multiple regression analyses showed that LVM was the most potent independent predictor of resting CBF in hypertension. Our results indicate that CBF, determined by thallium-201 myocardial scintigraphy, increases parallel to the increase in LVM, but unit CBF decreases even in the resting condition in patients with essential hypertension.

To elucidate left ventricular (LV) cardiac structure and function in patients with mild to moderate essential hypertension, we studied the relationship between LV geometry and function. We evaluated LV diastolic and systolic functions by M-mode echocardiography in 91 age-matched normotensive control subjects (NT) and 124 patients with essential hypertension. Hypertensive patients were divided into two groups based on the WHO stage classification: WHO I (n = 76) and WHO II (n = 48). Patients in WHO I and WHO II were further categorized according to the relative wall thickness as normal left ventricle (n = 47), concentric remodeling (n = 29), concentric hypertrophy (n = 25), and eccentric hypertrophy (n = 23). LV diastolic function was significantly decreased in the hypertensive groups compared to NT. There was no significant difference in LV systolic performance among NT, WHO I and WHO II. LV contractility was significantly increased in WHO I compared to NT. In respect to ventricular geometric pattern, LV diastolic function was significantly decreased in both the concentric hypertrophy and eccentric hypertrophy groups. LV systolic dysfunction was noted only in the eccentric hypertrophy group. In conclusion, patients with concentric remodeling had normal systolic and diastolic functions. LV diastolic function was impaired in both the concentric and eccentric hypertrophy groups due to an increase in LVMi. Moreover, LV systolic impairment was noted in the eccentric hypertrophy group due to an inappropriate compensation to LV systolic load.

Left ventricular elastance is the intrinsic mechanical property of the chambers that generates pressure for a given volume, but the dynamics of the ejection flow are characterized by the ventricular impulse in early systole. The purpose of this study was to characterize the ejection dynamics in the human hypertensive heart according to the concept of ventricular impulse and elastance. Nineteen hypertensive patients without left ventricular hypertrophy (HT-I), 42 hypertensive patients with left ventricular hypertrophy (HT-II), and 43 normotensive subjects (NT) were studied by pulsed Doppler echocardiography. The maximum ejection force (Fmax; kdyne) and the end-systolic wall stress/end-systolic volume index (ESWS/ESVI; kdyne/cm2/ml/m2)were examined as indexes of maximal impulse and elastance, respectively. Fmax was calculated on the basis of the unsteady Bernoulli equation. With regard to impulse and elastance in NT, Fmax was 43.7±6.1 and ESWS/ESVI was 2.26±0.78. In the hypertensive groups, HT-I showed normal Fmax (46.0±5.5) with a significantly higher ESWS/ESVI (3.52±1.12, p

To investigate the gender difference in the pathophysiology of essential hypertension, we investigated baroreflex sensitivity (BRS), aortic pulse wave velocity (PWV), blood pressure responses to mental arithmetic tests (MAT) and isometric handgrip exercise (IHG) in normotensive subjects (NT) and essential hypertensive patients (EHT) of both genders. EHT were classified as stage I (EHT-I) or stage II (EHT- II) according to the WHO stage classification. BRS in males tended to decline with increasing age and showed a significant (p

To elucidate the clinical significance of negative T wave on electrocardiogram in patients with essential hypertension, the relation between negative T wave and left ventricular mass (LVM) was studied in 89 patients with essential hypertension. Left ventricular hypertrophy was defined as an LVM index of equal to or greater than 125g/m2. Essential hypertensive patients were classified into the following three groups: Group I (n=46) with neither left ventricular hypertrophy nor a history of hypertensive heart failure, Group II (n=33) with left ventricular hypertrophy and without a history of hypertensive heart failure, and Group III (n=10) with both left ventricular hypertrophy and a history of hypertensive heart failure. Negative T waves in essential hypertensive patients were observed in 4.3% of Group I, 51.5% of Group II and 100% of Group III. LVM indices in Groups I, II and III were 97±18(g/m2), 151±20 (p

A monoclonal antibody against human renin was shown to recognize, by immunoblot, a 39kDa protein (possibly renin) in crude homogenates of several marmoset brain regions, and used to investigate the distribution of renin-like molecules in the brain by using light and electron microscopic immunohistochemistry. Cells with renin-like immunoreactivity were detected not only in hypothalamic nuclei and the parabrachial nuclei relevant to the control of blood pressure and water-electrolyte balance but also in other brain regions including the basal ganglia, basal magnocellular nucleus of Meynert, hippocampus, thalamus, midbrain, certain cranial nerve nuclei, raphe nuclei and the cerebellum. Preembedding electron microscopy demonstrated that renin-like Immunoreactivity was mainly present in neuronal perikarya and proximal dendrites and rarely in axon terminals and neuroglial components. The widespread and uneven localization of renin in marmoset brain may provide a morphological basis for certain central effects of renin and angiotensins injected into the cerebral ventricles. It is unlikely that brain renin is actively conveyed from neuronal soma to nerve endings. (Hypertens Res 1993; 16: 121-130)

Repeated oral doses (120mg or 240mg, once daily) of the human renin inhibitor ES-8891 were given for 10 days to 16 normotensive male subjects on a normal sodium diet. Both doses produced significant inhibition of plasma renin activity (complete inhibition at 0.5 and 1 hour, 50% inhibition at 2 hours) which was inversely correlated with the plasma level of ES-8891. Plasma immunoreactive active renin was not enhanced in spite of significant decreases in plasma angiotensin I and aldosterone levels. There was no significant change in blood pressure or heart rate. No adverse reactions were evident. These results suggest that ES-8891 is an orally active human renin inhibitor which may be clinically useful. (Hypertens Res 1992; 15: 41-44)

We studied the effect of a rat renin inhibitory peptide (RRIP) on kidney renin synthesis in spontaneously hypertensive rats (SHR). The RRIP was intraperitoneally administered (n=6) via an osmotic minipump to 11-week-old SHR for 7 days, at a rate of 10μg/kg/min. RRIP significantly reduced PRA and suppressed the elevation of systolic blood pressure in treated SHR compared to control. The content of kidney renin messenger RNA (mRNA) in treated SHR was comparable to that of control. Electron microscopic study revealed many renin granules and renin protogranules containing crystalline matrices in juxtaglomerular cells in RRIP-treated SHR. These results suggest that RRIP does not stimulate or suppress renin synthesis in the kidney. (Hypertens Res 1992; 15: 99-104)