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A 60-year-old Japanese man with obstructive hypertrophic cardiomyopathy was found to have a mutation in the cardiac myosin binding protein C gene: a single base deletion of a thymidine residue at nucleotide 11645 (codon 593) in exon 18. He was diagnosed at the age of 43 and has been followed for 17 years. During this follow-up period, echocardiograms and mechanocardiograms revealed progressive hypertrophy until the age of 54, then gradual dilation of the left ventricle associated with a decrease in the obstruction. Paroxysmal atrial fibrillation occurred at the age of 52 and progressed to chronic atrial fibrillation at the age of 53. He had congestive heart failure at the age of 58.

A patient with non-Q wave myocardial infarction had severe luminal narrowing in the first major septal perforator branch, which arose anomalously from the first diagonal branch. In this case, an exercise ECG showed a transient leftward QRS axis shift.

An 18-year-old male patient with biventricular hypertrophic obstructive cardiomyopathy (HOCM) had successful reduction of the pressure gradients by cibenzoline. At 11 months after birth, he was first diagnosed with cardiac murmurs and by the age of 5 years, he was diagnosed with subpulmonic infundibular stenosis with a pressure gradient of 10 mmHg by cardiac catheterization. At the age of 14, re-catherterization revealed hypertrophic cardiomyopathy with isolated obstruction of the right ventricular outflow tract, with a pressure gradient of 70 mmHg, but no obstruction in the left ventricle. He began daily treatment with 30 mg propranolol. At the age of 18, he was admitted for cardiac evaluation. An echocardiogram revealed left mid-ventricular and subpulmonic obstructions associated with pressure gradients of 88 mmHg and 65 mmHg, respectively. A single oral dose of 200 mg of cibenzoline decreased the pressure gradients in the left and right ventricles (38 mmHg and 36 mmHg, respectively). He was then given 300 mg daily of cibenzoline, and both pressure gradients remained low without any complications 8 months later at the time of discharge.

Insulin-like growth factor-1 (IGF-1) is important in the hypertrophic response of the myocardium, so the present study was designed to elucidate whether the circulating levels of IGF-1 and its binding proteins (IGFBPs) are related to the disease condition of patients with hypertrophic cardiomyopathy (HCM), in particular the occurrence of congestive heart failure (CHF). The study group comprised 124 patients with HCM and 15 healthy control subjects. The HCM patients were subdivided into 3 groups: 39 with hypertrophic obstructive cardiomyopathy (HOCM), 67 with hypertrophic non-obstructive cardiomyopathy (HNCM), and 18 with HCM and a history of CHF (HF-HCM, n=18). Serum levels of IGF-1 and IGFBPs (IGFBP-1 and -3) were compared between groups. IGF-1 levels were significantly higher in patients with HOCM and HNCM, and lower in patients with HF-HCM than in control subjects (p<0.0001, p<0.005, and p<0.05, respectively). IGFBP-1 levels were significantly higher in patients with HF-HCM than in the other 3 groups (p<0.0001 for all). The findings suggest that circulating levels of IGF-1 and IGFBP-1 are related to the extent of myocardial injury in patients with HCM.

Recent studies have demonstrated that elevated levels of cholesterol in the form of remnant-like particles (RLP-C) induce deterioration of endothelial function during the fasting state, but it is not known whether postprandial RLP-C elevation has the same effect. The objective of this study was to assess the effect of postprandial RLP-C elevation on endothelial function in 24 fasting normolipidemic subjects. Flow-mediated dilatation (FMD) during reactive hyperemia in the brachial artery was investigated. Serum lipids and lipoproteins during fasting and 4h after regular fat-loading were measured. Subjects were divided into 2 groups: the high responders (postprandial RLP-C level >7.5mg/dl, n=8) and the normal responders (postprandial RLP-C level < or =7.5mg/dl, n=16). Significant increases in the level of both triglycerides and RLP-C were observed in the high responders. Basal FMD in the high responders (4.3+/-3.0%) was significantly lower than that in the normal responders (8.3+/-2.4%) (p<0.01), but FMD after the fat-loading in both groups did not change significantly. The change in RLP-C levels during the fat-loading test correlated significantly with basal FMD (r=-0.588, p<0.01). Multiple regression analysis showed a significant correlation between basal FMD and the change in RLP-C levels (r=-0.488, p<0.02). The results of this study suggest that postprandial RLP-C elevation could be associated with atherosclerotic progression even in normolipidemic subjects.

Ischemic preconditioning (IP) and pretreatment with lipopolysaccharide (LPS) reduce myocardial infarct size, but the precise mechanisms remain unknown. Rats were divided into 3 groups: the Control (C) group was subjected to 30 min ischemia followed by 3 h reperfusion; the IP and LPS groups had the same ischemia-reperfusion (I-R) insult with either preconditioning stimuli or pretreatment with LPS, respectively. Infarct size was smaller in the IP (23.4+/-2.3% of risk zone size) and LPS groups (28.5+/-2.0% of risk zone size) than in the C group (52.3+/-3.4% of risk zone size). Nuclear factor kappa-B (NF-kappaB) binding activity increased at 30 min reperfusion and declined thereafter, then rose again at 3 h reperfusion in the C group. The values in the IP (362% of control) and LPS (324% of control) groups were higher before I-R, and then decreased from 30 min (46% and 64% of control, respectively) until 3 h reperfusion (22% and 36% of control, respectively). Nuclear staining of NF-kappaB after reperfusion was less in the IP and LPS groups than in the C group. Expressions of cytokine mRNAs (interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha) were detected 30 min after the onset of reperfusion and their levels remained high after 3 h of reperfusion. These expressions of cytokine mRNAs after I-R were substantially suppressed by IP and LPS, although IP and LPS alone induced modest expressions of these cytokine mRNAs. These data suggest that IP and LPS contribute to infarct size reduction via the downregulation of NF-kappaB and the attenuation of cytokine gene expression.

The effect of cibenzoline on left ventricular diastolic function was investigated in patients with hypertrophic cardiomyopathy (HCM). Before and 2 h after an oral administration of 200 mg of cibenzoline, echocardiographic, apexcardiographic and gated radionuclide angiographic studies were performed in 12 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 7 with hypertrophic nonobstructive cardiomyopathy (HNCM). After administration of cibenzoline, the left ventricular pressure gradient decreased from 96+/-33 mmHg to 29+/-22 mmHg (<0.0001). Fractional shortening decreased from 53.3+/-7.5 to 45.4+/-6.2% (p=0.0008) in patients with HOCM and from 49.9+/-8.7 to 40.9+/-7.5% (p=0.0039) in patients with HNCM. On the other hand, E-wave velocity increased and A-wave velocity decreased in both groups. The time between the second heart sound and O point was shortened from 253+/-53 to 176+/-21 ms (p<0.0001) in patients with HOCM and from 245+/-54 to 185+/-44 ms (p=0.0050) in patients with HNCM. The time to peak filling rate was shortened from 248+/-79 to 190+/-40 ms (p=0.0072) in patients with HOCM and from 218+/-33 to 163+/-26 ms (p=0.0052) in patients with HNCM. These results indicate that in patients with HCM, cibenzoline suppresses left ventricular systolic function, but can markedly improve left ventricular diastolic dysfunction through its direct action.

To evaluate whether or not beta-blockers can improve the condition of patients with heart failure treated with a combination of diuretics, digitalis and angiotensin-converting enzyme inhibitor (ACEI), 52 patients with chronic heart failure who have been treated with ACEI for more than 6 months were enrolled. They were divided into 2 groups: 26 patients continued the same therapy another 6 months or more (group A), and 26 patients were given oral metoprolol for 6 months or more, in addition to the ACEI (group B). Echocardiographic parameters and atrial and brain natriuretic peptides (ANP, BNP) were measured. The left ventricular dimensions at end-diastole and end-systole were significantly decreased and fractional shortening was significantly increased in group B after 6 months' treatment with the beta-blocker, but these parameters remained unchanged in group A. Plasma levels of both ANP and BNP were significantly decreased in group B, but remained unchanged in group A. These results indicate that concomitant beta-blocker therapy can improve left ventricular function and attenuate plasma ANP and BNP levels in patients with chronic heart failure treated with ACEI.

A 58-year-old male patient had apical hypertrophic cardiomyopathy (HCM) associated with a life-threatening tachycardia due to atrial flutter. Following palpitation and dyspnea for 2-3 h, he became unconscious because of circulatory catastrophe, but was fully resuscitated. An electrocardiogram recorded just before the loss of consciousness revealed atrial flutter at a rate of 260 beats/min with a 2:1 ventricular response. He was diagnosed as having apical HCM based on the echocardiographic and left ventriculographic findings. Atrial stimulation at a rate of 150 pacings/min for 1 min caused a marked drop in systemic systolic blood pressure from 170 to 120 mmHg. The patient was treated with 150 mg of cibenzoline per day to prevent supraventricular tachyarrhythmias and to improve left ventricular diastolic function. At the time of the recent follow-up at 2 and a half years, he felt quite well.

Dilated cardiomyopathy is an important cause of morbidity and mortality among patients with heart failure. Left ventricular dilation is viewed as a compensatory response to maintain stroke volume, and left ventricular dilation is directly related to the increase of wall stress. However, only a few studies have examined whether wall stress can be a prognostic variable in patients with dilated cardiomyopathy. This study was designed to elucidate whether left ventricular systolic wall stress was related to the prognosis in patients with dilated cardiomyopathy. Twenty-five normal control subjects and 68 patients with dilated cardiomyopathy participated in this study. Hemodynamic parameters and left ventricular systolic wall stress were determined using echocardiography. In addition, the extent score determined by thallium-201 myocardial scintigraphy was measured as an index of cumulative loss of myocardium. During the 53-month follow-up period, 13 patients died of cardiac events. In a stepwise multivariable analysis, end-systolic wall stress and fractional shortening were significant predictors of survival. The extent score was markedly greater in the patients who died than in alive patients. There was a significant correlation between end-systolic wall stress and extent score (r=0.501, p=0.0001). Left ventricular end-systolic wall stress is an important predictor of mortality in patients with dilated cardiomyopathy.

To examine the prognostic role of the circulating soluble form of Fas (sFas), circulating sFas levels were measured in 33 patients with dilated cardiomyopathy (DCM) and 12 age-matched normal control subjects (NC) using an enzyme-linked immunosorbent assay (ELISA). Circulating sFas levels in DCM were significantly higher than those in NC (2.42+/-1.02 vs 1.66+/-0.20 ng/ml, p=0.015). Patients with DCM were stratified into 2 groups [group I (n=15): sFas > or =2.06 ng/ml; group II (n=18): sFas <2.06 ng/ml] on the basis of the mean value plus 2SD of circulating sFas level in NC. The circulating sFas level was significantly increased in relation to the severity of heart failure and correlated positively to left ventricular end-diastolic pressure in DCM. However, there were no significant differences in left ventricular dimension between the 2 groups. There were 5 deaths from worsening heart failure in group II, but there were no deaths in group I during the follow-up period. In conclusion, circulating sFas levels were increased in patients with DCM. Circulating sFas levels are increased in proportion to the severity of heart failure and may provide prognostic information independent of left ventricular geometry.

A 57-year-old woman was admitted for examination because of chest discomfort. Transthoracic echocardiography was performed and she was diagnosed as having hypertrophic cardiomyopathy. An echocardiogram also revealed that she had midventricular obstruction with a pressure gradient of 125 mmHg determined by Doppler echocardiography. A phonocardiogram showed an early systolic sound and the beginning of the sound coincided with the time of septal-posterior wall contact. In addition, the timing also corresponded to the sudden obstruction of blood flow in the region of the midventricular narrowing. Furthermore, this sound markedly decreased with the reduction in pressure gradient caused by cibenzoline treatment. Thus, it was concluded that the early systolic sound was associated with midventricular obstruction and produced by a rapid deceleration of the interventricular flow caused by midventricular obstruction.

To elucidate whether the mode of left ventricular opacification using sonicated serum albumin (SSA) is dependent upon the severity of left ventricular dysfunction, SSA was administered intravenously to 26 patients with dilated cardiomyopathy, 24 patients with anteroseptal myocardial infarction, and 9 normal control subjects. The left ventricular inflow pattern in echocardiograms on the apical 4-chamber view was classified into 2 types: straight or whirling. The ratio of left ventricular opacified area to left ventricular end-diastolic area, called the percent left ventricular effective fraction (%LVEF), was also calculated. The inflow pattern was straight in all normal control subjects and 9 myocardial infarction patients, whereas 15 myocardial infarction and all dilated cardiomyopathy patients showed the whirling pattern. Percent LVEF was significantly smaller in patients with dilated cardiomyopathy (45 +/- 22%, p < 0.0001) and myocardial infarction (65 +/- 14%, p < 0.001) than in normal control subjects (84 +/- 7%). The area that was not opacified was observed only in the infarcted area in cases of myocardial infarction, and over wide regions in cases of dilated cardiomyopathy. In addition, there were significant correlations between %LVEF and ejection fraction or peak filling rate. These findings indicate that contrast echocardiography using SSA can reflect sensitively the severity of left ventricular dysfunctions and detect the regions involved in patients with dilated cardiomyopathy and myocardial infarction.

To assess the role of atrial and brain natriuretic peptides (ANP, BNP) in maintaining cardiac performance at rest and during exercise in patients with cardiac dysfunction, we measured plasma levels of ANP and BNP during 201Tl dynamic exercise testing in 32 patients with angiographically proven old myocardial infarction (OMI) and 35 normal control subjects (CS). Plasma levels of ANP and BNP at rest were significantly higher in patients with OMI than in CS (ANP, 42.6 +/- 19.3 vs 19.4 +/- 2.4 pg/ml, p < 0.01; BNP, 53.4 +/- 32.5 vs 2.8 +/- 0.8 pg/ml, p < 0.01, respectively). Correlations were found between plasma levels of these peptides and left ventricular ejection fraction (LVEF), cardiac index (CI), pulmonary capillary wedge pressure (PCWP) and left ventricular end-diastolic pressure (LVEDP) in patients with OMI. In addition, a strong positive correlation was found between plasma levels of these peptides and the severity score obtained from 201TI myocardial scintigraphy. During exercise, both ANP and BNP significantly increased in patients with OMI. However, in CS, although ANP increased, BNP remained unchanged. The changes in plasma levels of ANP or BNP from at rest to peak exercise correlated with LVEF, CI, PCWP, LVEDP and the severity score in patients with OMI. These findings indicate that ANP and BNP play an important role in maintaining cardiac performance at rest and during exercise in patients with cardiac dysfunction.

To elucidate the morphologic characteristics of the left ventricle in patients with hypertrophic cardiomyopathy who developed atrial fibrillation, we studied left ventricular geometry by two-dimensional echocardiography in 92 patients with hypertrophic cardiomyopathy. These patients were divided into two groups; 24 patients with transient or persistent atrial fibrillation (group I) and 68 patients with sinus rhythm (group II). Left ventricular chamber size in group I was significantly smaller than that in group II. Left ventricular chamber size was correlated positively with stroke volume, and was correlated negatively with left ventricular end-diastolic pressure. The incidence of systemic thromboembolism in group I was 7.1% per patient year. In hypertrophic cardiomyopathy, the size of the left ventricle appears to have major pathophysiologic significance in the development of atrial fibrillation. In addition, since patients with hypertrophic cardiomyopathy who develop atrial fibrillation have a potential risk of systemic thromboembolism, prophylactic anticoagulant therapy should be performed in these patients.

We present a patient with metastatic cardiac leiomyosarcoma that was diagnosed antemortem by transesophageal echocardiography (TEE) and ECG-gated magnetic resonance imaging with gadolinium diethylene triaminepentaacetic acid (Gd-DTPA MRI). TEE and Gd-DTPA MRI clearly revealed the morphological characteristics of infundibular stenosis and cardiac tamponade. Our patient has survived about 30 months after cardiac surgery. Since sarcoma is usually associated with a very poor prognosis, surgical treatment should be performed as soon as possible. TEE with color Doppler imaging and Gd-DTPA MRI are very useful diagnostic methods for determining the precise anatomical characterization of cardiac tumor, and these procedures are prerequisite to precise therapy.

A 62-year-old patient was admitted to our hospital for treatment of early gastric cancer. After total gastrectomy, he suffered from anteroseptal myocardial infarction. Systolic anterior motion of the mitral valve which was not observed before surgery was observed during the acute phase of myocardial infarction and completely disappeared 3 weeks after the onset of myocardial infarction. Systolic anterior motion of the mitral valve in this patient may have been caused by changes in left ventricular wall motion during the acute phase of myocardial infarction.

To determine the common morphological characteristics of hypertrophic cardiomyopathy (HCM) by ventriculography from a right anterior oblique projection, diaphragmatic and free wall configurations were analyzed in 15 patients with obstructive HCM (HOCM), 32 patients with nonobstructive HCM (HNCM) and 17 controls. There was a convexity extending into the left ventricle in the right anterior oblique projection due to hypertrophy of the interventricular septum (IVS) in all patients with HCM. The peak convexity, where septal thickness was maximal (M point), was closer to the base in HOCM than in HNCM. Due to this convexity, the left ventricle showed a catenoid-shaped distortion at the M point. The distortion was severer in HOCM than in HNCM. Left ventricular free wall (LVFW) thickness was measured at the base and near the apex. LVFW thickness in HOCM decreased toward the apex, similar to that in controls, but in 17 of 32 HNCM (53%) LVFW thickness increased toward the apex. Cardiac index and stroke index in HCM were significantly smaller than those in controls. There was a significant correlation between the position of the M point and stroke index in HCM. These results indicate that a common morphological characteristic of HCM on the diaphragmatic side is the existence of a convexity extending into the left ventricle, and that cardiac performance in HCM is greatly influenced by the nature of the convexity. Myocardial abnormality seems to exist primarily at the base of the IVS in HOCM, and primarily in the lower part of the IVS and LVFW in HNCM.

This report presents a case of aortic valvular dysfunction and right coronary artery disease following radiation therapy on the mediastinum. A 61-year-old woman had received mediastinal radiation for the treatment of right mammary cancer 20 years previously. She developed symptoms of congestive heart failure 6 months ago. The patient was found to have aortic valvular dysfunction and proximal stenosis of the right coronary artery. Surgical aortic valve replacement improved cardiac status, and vasodilator treatment reduced ischemia due to right coronary artery stenosis.

A 72-year-old female who underwent the extirpation of metastatic intraspinal tumor showed an extremely wide variation of blood pressure with recurrent episodes of syncope due to paroxysmal hypotension. Treatment of the patient with salt supplement and L-threo-3, 4-dihydroxyphenylserine, an exogenous precursor of norepinephrine, markedly improved the syncopal attack as well as the daily activity.

The effect of chronic catecholamine excess on cardiac function was assessed in 8 patients with surgically proven pheochromocytoma and the results compared with data obtained from normal controls and essential hypertensives. Major findings in systolic time intervals (STI) in patients with pheochromocytoma were a marked shortening of electromechanical systole and left ventricular ejection time (ET), but pre-ejection period (PEP) remained within normal limits. These findings were not altered by correction for heart rate. The ET/PEP ratio was very low (1.87 +/- 0.31) due to the remarkable shortening of ET. The ET/PEP ratio in essential hypertensives was also low (1.77 +/- 0.38), but this was mainly due to a remarkable prolongation of PEP. Low cardiac index, low stroke index and high total peripheral resistance index were preoperative characteristics in patients with pheochromocytoma, but returned to normal after operation. These results suggest that chronic excessive production of catecholamines from pheochromocytoma has deleterious effects on the heart, and that wide differences in STI exist between patients with pheochromocytoma and those with essential hypertension.

In 1977, 92 male patients with mild hypertension (persistent diastolic blood pressure between 90 and 104 mmHg) were found from among 1608 men aged between 18 and 40 years old who were employees of an industrial company. Of these, 81 patients were followed-up for 10 years. After that time, blood pressures (BP) of 44.4% of the mild hypertensive patients became normotensive (group N); BP of 22.2% remained mild hypertensive (group M); and BP of 33.4% increased to higher levels than the starting BP (group H). Higher levels of systolic and diastolic BP, a higher incidence of family history of hypertension, a higher voltage of SV1 + RV5 on ECG and a lower concentration of serum triglycerides at the starting point were risk factors for the progression to higher levels of hypertension. Body weights of patients in group H increased significantly during the follow-up period. These results indicate that male mild hypertensive patients with the above-mentioned risk factors should be followed carefully, especially with regard to increased body weights.

A 17-year-old female patient with hypertrophic cardiomyopathy whose serum cardiac enzymes (creatine phosphokinase = CPK, lactic dehydrogenase = LDH) showed persistent elevation was presented. Percent of CPK-MB and LDH1 in 6-year-follow-up period ranged from 3.2% to 8.5%, and 58.0% to 63.2%, respectively. This finding strongly suggests the existence of a small amount of continuous myocardial necrosis for a long time. The influence of cardiac enzyme release on the heart was assessed by serial checks of electrocardiogram, echocardiogram and 201-thallium myocardial scintigram. In serial checks of electrocardiograms, markedly decreased R wave amplitude ranging between 31% and 47% was observed in II, III, aVF and V3-6. On echocardiograms, asymmetric septal hypertrophy and a narrow left ventricular cavity were observed in all echocardiograms through the follow-up period. But, in most recent apical two-dimensional echocardiograms, hourglass appearance of the left ventricle due to a distinct cavity-formation at the apex was observed. In 201-thallium single photon emission computed tomogram, hypoperfusion area markedly extended in anterior and lateral parts. These changes in electrocardiograms, echocardiograms and 201-thallium myocardial scintigrams seemed to reflect myocardial necrosis. Our case points to a mechanism for hypertrophic cardiomyopathy to change, over time, to dilated cardiomyopathy-like features.

The possible existence of prorenin (inactive form of renin) in rabbit renal cortex was studied. Renal cortex was homogenized with 0.25 M sucrose. Following centrifugation at 800 g for 10 min, the supernatant (Fraction H) was centrifuged at 20,000 g for 20 min. The pellet (Fraction G) was separated from soluble fraction (Fraction S). Intravenous injection of non-treated Fraction G caused a little blood pressure elevation in rats. However, the pressor activity of the same amount of Fraction G which was frozen and thawed 5 times previously was more than 10 times as that of non-treated one. The renin activity in preincubated fraction G with Fraction S was 2-fold the summation of the activity of renin in each fraction, when measured using indirect method. Fraction S lost not only the renin activity but also the renin activating activity when heated for 5 min at 100 degrees C. Exposure to pH 3.5 made no influence on renin activity in either Fraction G and S.

The effects of angiotensin II, thyroxine and 17 beta estradiol on plasma renin substrate concentration in rats and renin substrate production by perfused rat livers were investigated. The addition of angiotensin II (1-10 microgram) to the perfusion system did not affect the synthesis of renin substrate. After treatment with thyroxine (2.5 mg/kg/day), plasma renin substrate concentration, plasma renin activity, plasma aldosterone concentration and the rate of renin substrate synthesis were all significantly increased. 17 beta estradiol (2 mg) raised both plasma renin substrate concentration and the amount of renin substrate production by the liver. Isoelectric focusing profiles of renin substrate of liver perfusate and of plasma from estrogen-treated rats were different from that of liver perfusate from normal rats. But the profile of renin substrate in plasma was essentially similar to those to liver perfusates both in normal and estrogen-treated rats.

Measurement of plasma renin concentration (PRC) was done in normal subjects at rest and under acute stimulation of renin release under unrestricted sodium intake. Concurrent measurements of plasma renin activity (PRA) and plasma aldosterone concentration (PA) were carried out. The mean values of PRC at rest and after stimulation of renin release were 12.8 +/- 1.3 (SEM) and 21.7 +/- 4.4 (SEM) ng AT I/ml/h, respectively. These corresponded to renin contents of 3.4 +/- 0.34 (SEM) X 10(-5) Goldblatt units and 5.8 +/- 0.36 (SEM) respectively. The mean percent increase of PRC (82.1 +/- 19.3 (SEM)) %) was almost indentical to that of PA (81.5 +/- 16.4 (SEM) %), but differed from that of PRA (269 +/- 83.1 (SEM) %). A very high correlation between concurrent PRC and PA (r = 0.92, P less than 0.001) was found in normal subjects at rest and under acute stimulation of renin release. A good correlation between PRC and PRA (r = 0.85, P less than 0.001) was also observed. However, a higher correlation between percent increases of PRC and PA (r = 0.92, P less than 0.001) than that of PRA and PA (r = 0.80, 0.01 less than P less than 0.005) was found. Results show that PRA is a good index of the renin content in plasma in normal subjects at rest and PRC reflects actual renin concentration in plasma at rest as well as under stimulation of renin release.

The aim of this study was to examine the impact of a family history of hypertension (FHH) on blood pressure levels in Japanese rural adolescents. The study population consisted of 458 and 553 subjects, aged 13 and 16 years, respectively. Particular attention was focussed on subjects with a FHH (13 years old, n = 38; 16 years old, n = 46) and those without a FHH (13 years old, n = 83; 16 years old, n = 97). Significant associations were found between FHH and systolic blood pressure for boys and girls at 16 years old and diastolic blood pressure for girls at 16 years old. The impact of a FHH on blood pressure mainly affected systolic blood pressure in late adolescence (16 years of age). In early adolescence (13 years of age), different physical maturation status may have masked the real impact of a FHH on blood pressure.

Human renin substrate (angiotensinogen) was purified from outdated bank plasma. Purification procedures included ammonium sulfate precipitation, DEAE-cellulose column chromatography, concanavalin A-Sepharose column chromatography, Hydroxylapatite column chromatography preparative isoelectric focusing and Ultrogel AcA 44 gel filtration. The final recovery was 10% and the specific angiotensin I content of 10.5 micrograms/mg of protein was obtained. Polyacrylamide gel and SDS-polyacrylamide gel electrophoresis and analytical ultracentrifugal analyses showed the homogeneity of the purified renin substrate. The molecular weight of 60900 was determined by sedimentation equilibrium studies. Human renin substrate was a glycoprotein containing 13% carbohydrate. Cystine could not be detected on amino acid analysis. The purified renin substrate showed the isoelectric point heterogeneity (pI, 4.6 and 4.9).

The blood pressures (BP) and anthropometric values of 1,014 Japanese rural school children aged 12-17 years old were measured at one-year interval. The strongest correlation for systolic BP (SBP) was weight and for diastolic BP (DBP) it was age. Larger values of weight, body mass index, triceps skinfold thickness and smaller increment of height showed significant discriminative powers in differentiating the subjects who had been above the age-sex specific 80th percentile value (H-H group) from those who had been below the 20th percentile value (L-L group) for both SBP and DBP. Subjects with a family history of hypertension (FHH) had higher SBP than those without a FHH, and were more prevalent in H-H group for SBP. These results indicate that larger body size and more mature stature are determinants of higher levels of BP during adolescence, and that FHH affects SBP only in this period.

By treating human plasma with trypsin (1 mg/ml), 3 different peaks of renin activity were detected by a gel filtration on Ultrogel AcA 44. The molecular weights of these activated renins were estimated to be 47,000, 45,000 and 43,000 daltons, respectively. 2) The molecular weight of human plasma active renin partially purified was 43,000 daltons. After treatment with neuraminidase, the molecular weight decreased to 38,000 daltons. 3) When the partially purified plasma inactive renin, which was completely separated from active renin, was activated by trypsin, chymotrypsin, plasmin, pepsin and renin, the activated renins had different molecular weights. The highest molecular weight form (47,000-48,000) was trypsin-activated or plasmin-activated renin and the lowest molecular weight form (38,000) was renin-activated renin. 4) These results suggest that cleavage of the specific site in peptide bond of plasma inactive renin by various proteolytic enzymes results in different molecular weights of activated renins. Plasma active renin free from sialic acid is very similar to kidney renin.

Hemodynamic changes during the cold pressor test were examined in Type I labile (juvenile labile) hypertensive patients, Type II labile (middle aged labile) hypertensive patients, established hypertensive patients and normal subjects. In normal, Type I labile hypertensive and established hypertensive subjects, the pressor response during the test was accounted for chiefly by a rise in peripheral resistance. In Type II labile hypertensive patients, an increase in blood pressure during cold stimuli was accompanied by an augmented cardiac output. Therefore, Type II labile hypertension is separated clearly from other types of hypertension with respect to hemodynamic changes during the test. In Type II labile hypertensive patients, however, diazepam reduced an increase in cardiac output during the test, resulting in hemodynamic changes similar to those of normal subjects. After atropinization, the hemodynamic pattern of Type I and established hypertensives changed similar to that of Type II labile patients during the cold pressor test. It is concluded that an excessive cardiac output caused by the cold stimuli is a distinctive hemodynamic characteristics of Type II labile hypertensive patients, and this distinctive hemodynamic characteristics might be due to the decreased parasympathetic tone.

We homogeneously purified human renin substrate from outdated bank plasma and raised antibody against it. The antibody did not cross-react with angiotensin I, angiotensin II or synthetic tetradecapeptide at concentrations of up to 160 nmol, nor did it cross-react with up to 0.2 ml of plasma from rat, rabbit or sheep. It did, however, completely cross-react with human des-angiotensin I renin substrate. A direct radioimmunoassay for human renin substrate was developed using the antibody, and the minimum detectable value of renin substrate found to be 70 pg of protein. Plasma renin substrate concentrations of normal subjects, essential hypertensive patients, diabetic patients and pregnant women were measured by direct and indirect assays. Hypertensive patients had similar concentrations of plasma renin substrate to normal subjects, whereas diabetic patients had significantly lower plasma renin substrate concentrations (p less than 0.01). The direct assay always gave a higher value than the indirect assay, and the ratios of the two assays (direct assay/indirect assay) were similar in normal subjects, hypertensive patients, diabetic patients and pregnant women.

Hemodynamic responses and behaviors of the renin-angiotensin-aldosterone system to a single administration of captopril (50 mg) were studied in 16 hypertensive patients (essential hypertension, n = 10; renovascular hypertension, n = 3; primary aldosteronism, n = 2; Cushing's syndrome, n = 1). In 10 essential hypertensive patients, the immediate blood pressure reduction caused by decreased total peripheral resistance after the administration of captopril was observed without changes of cardiac output and heart rate. Serum angiotensin converting enzyme activity and plasma aldosterone concentration significantly decreased, whereas plasma renin activity significantly elevated 2 hours after the administration of captopril. The close relationship between the pretreatment value of plasma renin activity and the maximum decrease in mean blood pressure in 16 hypertensive patients suggests that the depressor response to a single administration of captopril could evaluate the degree of angiotensin II dependency in the maintenance of high blood pressure in various types of hypertension.