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Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome is a rare Mullerian duct anomaly characterized by an obstructed hemivagina, ipsilateral renal agenesis, and uterine didelphys. There are only a few published case reports of OHVIRA syndrome, and cases of OHVIRA syndrome associated with cancer have rarely been reported. In fact, there is only one published report of a case with clear cell carcinoma (CCC) of the cervix. Here, we report a case of CCC of the cervix with OHVIRA syndrome that underwent abdominal radical hysterectomy; we also provide a short literature review of this topic. A 52-year-old woman presented with abnormal vaginal bleeding for 1 month 2 years after menopause. A pelvic examination and preoperative imaging showed uterine didelphys, an obstructed hemivagina with a mass measuring approximately 2 cm located in her left cervix, and an absence of her left kidney. A colposcopy biopsy reported CCC of the cervix. Clinical staging classified her with stage IB1 disease. Abdominal radical hysterectomy was performed. Her left ectopic ureter led to the left cervix and opened in the endometrium, resulting in a so-called ectopic ureter. Macroscopic examination of the excised specimens showed two cervixes, two corpora of the uterus, and a tumor measuring 1.0 × 2.0 cm on the left cervix. In addition to typical OHVIRA symptoms including uterine didelphys, obstructed hemivagina, and renal agenesis, several anatomical variants were present. The current case included those variants as well as an atrophic kidney with an ectopic ureter to the obstructed hemivagina. Based on the results of our case, clinicians should be aware of the risks of cancer and anatomical variants associated with OHVIRA syndrome.

Uterine sarcomas with myomelanocytic differentiation have been reported to be diagnostically challenging. We report a case of uterine leiomyosarcoma with extensive perivascular epithelioid cell tumor (PEComa)-like areas and extrauterine metastases. The patient was a 49-year-old gravida 3 para 2 Japanese woman with no relevant medical history. She noticed a vaginal mass with bleeding. Imaging examination revealed a uterine tumor and multiple liver and lung metastases. The vaginal tumor (3.5 cm) was resected and diagnosed as a malignant PEComa based on morphology and myomelanocytic marker expression. Clinically used targeted sequencing (FoundationOneCDx™) revealed gene alterations in RB1, TP53, and ATRX but not TSC1/2. Despite administration of an mTOR inhibitor, the tumor size increased, and subsequently, hysterectomy was performed to relieve the symptoms. The uterine tumor was composed of conventional leiomyosarcoma showing RB1 loss, wild-type TP53 staining, and retained ATRX expression, as well as adjacent predominant PEComa-like components with RB1 loss, TP53 overexpression, and ATRX loss, identical to the characteristics of the vaginal tumor. In the uterine tumor, both HMB-45 and MITF were weak to moderately positive for approximately 40% of tumor cells while Melan-A was negative. The tumor was finally diagnosed as leiomyosarcoma with PEComa-like features. This case exemplifies the tumorigenesis of diagnostically challenging tumors with myomelanocytic differentiation and demonstrates the importance of integrating multiple types of information, including genomic profiling, in making a correct diagnosis leading to appropriate treatment.

Four major morphologically distinct classes of cells were identified within the adult rabbit meniscus using antibodies to cytoskeletal proteins. Two classes of cell were present in the fibrocartilage region of the meniscus. These meniscal cells exhibited long cellular processes that extended from the cell body. A third cell type found in the inner hyaline-like region of the meniscus had a rounded form and lacked projections. A fourth cell type with a fusiform shape and no cytoplasmic projections was found along the superficial regions of the meniscus. Using a monoclonal antibody to connexin 43, numerous gap junctions were observed in the fibrocartilage region, whereas none were seen in cells either from the hyaline-like or the superficial zones of the meniscus. The majority of the cells within the meniscus exhibited other specific features such as primary cilia and 2 centrosomes. The placement of the meniscal cell subtypes as well as their morphology and architecture support the supposition that their specific characteristics underlie the ability of the meniscus to respond to different types of environmental mechanical loads.

A study was conducted to determine whether sympathetic nerve activity, one of the main regulators of blood pressure, is involved in high blood pressure in the night-time and morning. Twenty-seven untreated hypertensive subjects, in whom hypertension was diagnosed by ambulatory blood pressure (ABP) measurement, who showed a 24 h systolic ABP value over 140 mmHg and/or 24 h diastolic ABP over 90 mmHg were recruited. They also showed a night-time systolic ABP value of over 130 mmHg and/or a night-time diastolic ABP of over 80 mmHg. They were divided into two groups: "dippers (D)" whose night-time ambulatory blood pressure fell by more than 10% of the day-time blood pressure, and "non-dippers (ND)" in whom this phenomenon was absent. We examined the effect of a long-acting alpha 1-blocker (doxazosin) on diurnal blood pressure variation in these subjects with essential hypertension. Baseline casual blood pressure and 24 h systolic ABP were not significantly different between the two groups. However, both night-time and morning ABP in ND were higher than those in D. Administration of doxazosin (mean 73 +/- 13 (SE) d) significantly decreased casual blood pressure, and 24 h, day-time, night-time and morning systolic ABP in the whole cohort. When subjects were divided into D and ND, the day-time and morning systolic ABP decreased significantly after doxazosin treatment in both groups, whereas the night-time systolic ABP decreased significantly only in ND but not in D. These results suggest that sympathetic nerve activity involved in elevating blood pressure during the night may differ between D and ND.

OBJECTIVE To clarify the role of calcium-binding proteins (CaBP) in hypertension. DESIGN CaBP from several organs of spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats were purified and their characteristics compared between the two strains. The CaBP were purified by applying the soluble cytosolic fractions from mesenteric vessels, heart, kidney and brain of 4- and 10-week-old SHR and WKY rats to a phenyl-Sepharose column. Felodipine binding to the purified CaBP was then measured. RESULTS The fluorescence intensity of felodipine increased in a calcium-dependent manner when it bound to CaBP. The pK 0.5 Ca2+ values derived from the calcium ion-felodipine fluorescence curves for each CaBP preparation from organs of the two strains were similar, indicating that the calcium sensitivities of the CaBP to the felodipine binding process are similar in SHR and WKY rats. In 10-week-old SHR the mean levels of felodipine-bound CaBP in heart, brain and kidney were significantly altered compared with those in WKY rats. No such alterations were observed in heart, kidney and brain from 4-week-old SHR and WKY rats. Conversely, the mean levels of felodipine-bound CaBP in mesenteric vessels from 4- and 10-week-old SHR were reduced significantly compared with those of age-matched WKY rats. CONCLUSIONS These results suggest that the levels of cytosolic felodipine-bound CaBP from heart, kidney and brain are altered in response to elevated blood pressure, and that reduced levels of felodipine-bound CaBP in the mesenteric vessels of SHR might be a primary characteristic of this rat strain.

We encountered a case of dystrophin-verified Becker muscular dystrophy which exhibited left heart failure as an initial symptom but no subjective muscle weakness. Severe cardiac involvement has been thought to rarely occur in the early stage of this disease, however accurate diagnosis was limited until the dystrophin diagnosis became available. This case suggests that some cases of dilated cardiomyopathy might be Becker muscular dystrophy, and that dystrophin tests should be added to the conventional investigation of patients with dilated cardiomyopathy.(Internal Medicine 32: 408-411, 1993)

The Watanabe Heritable Hyperlipidemic (WHHL) rabbit is a widely studied animal model for the human genetic disorder familial hypercholesterolemia, and spontaneously develops atherosclerotic disease. We studied the growth characteristics of cultured vascular smooth muscle cells (VSMC) from WHHL rabbits compared with VSMC from Japanese white rabbits. We measured cell proliferation, DNA synthesis, and c-myc proto-oncogene expression, in response to growth stimuli such as fetal bovine serum (FBS) and platelet-derived growth factor (PDGF). VSMC from Japanese white rabbits exhibited a 4-fold increase in cell numbers during a 5-day incubation period compared with those from WHHL rabbits. FBS and PDGF stimulated DNA synthesis, as measured by thymidine incorporation into VSMC, in both Japanese white rabbits and WHHL rabbits, however the response was significantly higher in the former strain. The intracellular pH value of VSMC determined using the pH-sensitive fluorescence dye 2′,7′-bis-carboxyethyl-carboxyfluorescein was significantly higher in WHHL rabbits than in Japanese white rabbits. Proto-oncogene c-myc was induced by exposure of VSMC to FBS, however there was no significant difference in c-myc mRNA levels between the two strains. These results suggest that VSMC from WHHL rabbits are not genetically growth accelerated, but show decreased growth response to growth stimuli.

This study was designed to evaluate left coronary vascular bed reserve in hypertensive cardiac hypertrophy. The subjects were eight patients with hypertensive cardiac hypertrophy (HT) and nine patients with normal coronary flow (N). Coronary sinus flow (CSF) was measured by a continuous thermodilution method, and the ascorbic acid-platinum reaction was employed for the mean transit time measurement (T0-T2) of left coronary flow. T0 is ascorbic acid injection into the left coronary orifice and T2 is the maximal point of detecting ascorbic acid volume in the coronary sinus. Volumes for the coronary vascular bed (CVB) were obtained by multiplying CSF and T0-T2. CVB value in the HT patients was more than that in the control group at control heart rate, but was less than in N at a high pacing rate. CSF in the HT patients was more than that in the N group at any heart rate, and the CVB values per unit of myocardial mass were less in the HT patients than in the N group. The pressure rate product in the HT patients was more than that in the normal coronary flow group. The transit time of left coronary flow in the HT patients was less than that in the N group. The CVB in the HT group was more than that in the normal coronary group at control heart rate and less than that in the normal group at a high pacing rate. Cardiac work in the HT patient was thus shown to be greater than that in the normal group.

To explore the role of calcium channels in hypertension, dihydropyridine ([3H]PN200-110) binding to heart, brain, and skeletal muscle microsomes of 4-, 8- and 15-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was measured. At a constant Ca2+ ion concentration (pCa 3.0), maximal binding (Bmax) of dihydropyridine binding to heart and brain microsomes was significantly enhanced in 8- and 15-week-old SHR compared with WKY rats (p less than 0.01), whereas this phenomenon was not observed in 4-week-old SHR and WKY rats. Bmax and dissociation constant (Kd) values for skeletal muscle microsomes from SHR showed no difference compared with WKY rats irrespective of age. Dihydropyridine binding to heart microsomes, brain microsomes, and solubilized skeletal muscle microsomes exhibited strong calcium dependence. The Ca2(+)-dependent dihydropyridine binding curves for heart showed a Hill slope, and pK 0.5 values for 15-week-old SHR and WKY rats were 0.70 +/- 0.12 and 4.66 +/- 0.12 versus 0.72 +/- 0.12 and 5.66 +/- 0.08 (n = 4, mean +/- SD), respectively, indicating that 15-week-old SHR require 10-fold higher calcium concentration than WKY rats to promote dihydropyridine binding. The pK 0.5 values of calcium for brain and solubilized skeletal muscle calcium channels in 15-week-old SHR were also significantly lower than in WKY rats. This difference first became apparent in SHR and WKY rats as early as 4 and 8 weeks after birth. These results suggest that enhancement of calcium channel density might occur in the heart and brain of SHR in response to elevated blood pressure and that reduced calcium sensitivity of dihydropyridine binding to calcium channels might be a primary characteristic of this rat strain.

We investigated, by case-control study, the relevance of psychosocial factors on the prevalence of acute ischemic heart disease (IHD) in middle aged Japanese men. We questioned 109 acute IHD patients and 80 individuals in an age-adjusted sampled control group. Multiple logistic regression analysis showed the following statistically significant factors: hypertension (odds ratio 4.01, p less than 0.001), Type A behavior pattern (2.25, p less than 0.05) and high job demand (2.23, p less than 0.02). No direct influence of family function or social support to the prevalence of acute IHD was apparent. These results suggest that, among men in Japan, Type A behavior pattern and high job demand represent psychosocial risk factors of IHD. Due to the case-control protocol, causal relationships cannot be decided. The limitation of the study design is discussed within that context.

OBJECTIVE: To examine whether changes in calcium-binding proteins, one of the components of the calcium ion handling mechanism, occur in humans with essential hypertension. DESIGN: We measured the levels of cytosolic calcium-binding proteins purified from human erythrocytes using a felodipine fluorescence assay, and examined the correlation between this parameter and the ambulatory blood pressure (ABP). We divided 127 subjects into four age-matched groups according to their mean ABP levels and whether they had a family history of both hypertension and stroke [group A hypertensives with a positive family history (n = 30), group B hypertensives with no family history (n = 31), group C normotensives with a family history (n = 31) and group D normotensives with no family history (n = 35) of hypertension and stroke]. RESULTS: The erythrocyte cytosolic level of calcium-binding proteins in group A was significantly lower than that in group B, as was that in group C compared with group D. There was no significant correlation between the erythrocyte level of calcium-binding proteins and casual blood pressure values in any group. However, in group A significant negative correlations between the erythrocyte level of calcium-binding proteins and systolic and mean ABP were observed (r = -0.34, P < 0.05 and r = -0.39, P < 0.05, respectively). No significant correlations between the ABP and erythrocyte levels of calcium-binding proteins were observed in the other groups. When each group was subdivided according to sex, there were significant negative correlations between the erythrocyte level of calcium-binding proteins and the systolic and mean ABP in the males of groups A and C, but no correlations were found in any of the female subgroups or the males of groups B and D. Reducing the blood pressure by antihypertensive drug therapy did not affect the erythrocyte calcium-binding proteins level in 13 patients from groups A and B. Analysis using anion-exchange fast-performance liquid chromatography on a Mono-Q column and sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed that the calcium-binding proteins in human erythrocytes, the levels of which were low in group A, formed a single protein band with a molecular weight of 17,000, which was assumed to be a calmodulin. CONCLUSIONS: These results suggest that there are subgroups of hypertensive patients with low erythrocyte cytosolic levels of calcium-binding proteins, which are genetically determined. Furthermore, our data suggest that the erythrocyte level of calcium-binding proteins and ABP in male subjects with hypertension and normotensives with a genetic predisposition are correlated strongly, whereas no such correlation was observed in any female subgroup. This indicates that the regulatory mechanism or mechanisms involved in the control of blood pressure in men and women may be different.

The physiological and pathophysiological roles of protein kinase C activation were investigated in cultured mouse myocardial cells. First, effects of 12-O-tetra-decanoyl-phorbol-13-acetate (TPA), a potent activator of protein kinase C, on the intracellular pH (pHi) and cytosolic free Ca2+ level [( Ca2+]i) were studied, using 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) and quin-2, respectively. In the presence of the Ca ionophore A23187, TPA induced a rise in pHi by activating amiloride-sensitive Na+/H+ exchange and also produced a rise in [Ca2+]i above that seen with A23187 alone. These effects were totally inhibited by amiloride. Second, the effect of TPA on hypoxia-induced myocardial cell injury was evaluated. The addition of TPA to the culture medium enhanced creatine kinase release from hypoxic myocardial cells (95% N2 + 5% CO2). This effect was markedly suppressed by the addition of amiloride. These data suggests that protein kinase C activation aggravates hypoxic myocardial injury, presumably by inducing Ca2+ overload. This event is secondary to activation of Na+/Ca2+ exchange through accelerated influx of Na+ into the cells as a result of Na+/H+ exchange stimulation by protein kinase C.

Major and minor axes of the left ventricle were measured by single beam echocardiography in ten cardiac patients and the measurements and calculated volumes by formula V=pi/6 D2 were compared with the angiocardiographic estimates. There was a favorable correlation between echocardiographic and angiocardiographic major axis dimention (r=0.79), left end-diastolic volume (r=0.96), and ejection fraction (r=0.81). On the contrary, left end-diastolic volume calculated by formula V=D3 was less correlated with angiocardiographic estimates (r=0.93) and the former had a tendency to overestimate the volumes where D exceeded 6.5 cm. These data indicate that in cases with markedly enlarged left ventricle, the use of formula V=pi/6 D2L is a more accurate predictor of volumes than formula V=D3.

The concept of left atrial systolic time intervals anil Doppler echocardiography were used in a quantitative assessment of left atrial function in relation to the presence or absence of a fourth heart sound and to left ventricular hypertrophy in 47 patients with hypertension. Left atrial systolic time interval indexes included atrial pre-ejection period (the time between the onset of an electrocardipgraphic P wave and the onset of left ventricular inflow during atrial systole [A wave]), corrected atrial pre-ejcctlon period (the airial pre-ejection period divided by the duration of the P wave), and atrial ejection time (the time between the onset and cessation of the A wave).Twenty-one patients with a fourth heart sound on the phonocardiogram had a shorter atrial pre-ejection period (81 ± 10 versus 89 ± 14 ms p < 0.05) and a corrected atrial pre-ejection period (66 ± 17 versus 83 ± 18 ms, p < 0.01), as well as a longer atrial ejection time (147 ± 15 versus 126 ± 13 ms, p < 0.001) than did 26 patients without a fourth heart sound. The ratio of atrial pre-ejection period to atrial ejection time and that of corrected atrial pre-ejection period to atrial ejection time was smaller in patients with than in patients without a fourth heart sound (0.56 ± 0.08 versus 0.71 ± 0.11, p < 0.001; 0.46 ± 0.16 ms−1versus 0.67 ± 0.17 ms−1, p < 0.001, respectively). Left ventricular wall thickness (the sum of interventricular septal thickness and left ventricular posterior wall thickness) evaluated by two-dimensional echocardiography correlated positively with left atrial ejection time (r = 0.42, p < 0.01) and negatively with corrected atrial pre-ejection period (r = −0.34, p < 0.02), the ratio of atrial pre-ejection period to atrial ejection time (r = − 0.35, p < 0.02) and the ratio of corrected atrial pre-ejection period to atrial ejection time (r = −0.40, p < 0.01).It is concluded that quantitative evaluation of left atrial function obtained by left atrial systolic time intervals correlates with the presence of a fourth heart sound and with left ventricular wall thickness.

Rapid cyclic fluctuations of blood pressure in patients with a pheochromocytoma have rarely been reported. The suitable conditions to induce this phenomenon are not adequately known. We report here a patient with an adrenal pheochromocytoma who showed this phenomenon after oral administration of labetalol.

The perfusion territories in polar representations of stress Tl-201 rotational myocardial imaging in patients with angina pectoris who had one diseased coronary segment were analyzed. The lesions proximal or distal to the first major septal perforator in left anterior descending arteries were detected by the presence or absence of defects at the base of the anterior septum. Right coronary artery lesions were detected by the presence of defects at the basal posterior septum, in contrast to the preservation of myocardial uptake at this portion in lesions of the left circumflex artery. The specific defect patterns were detected in cases with lesions at the first diagonal, obtuse marginal, and posterolateral branches. Recognition of these defects in the polar maps allows detailed detection of diseased coronary arterial branches.

An elderly woman with Lutembacher's syndrome remained asymptomatic until the age of 55, when she was treated for exertional dyspnea with digitalis and diuretics. She died of gastrointestinal hemorrhage and hepatic failure at the age of 69. The autopsy revealed a large atrial septal defect and mitral stenosis without rheumatic changes. This patient is the oldest reported survivor of Lutembacher's syndrome with nonrheumatic mitral stenosis.

Myocardial ischaemia induces cytosolic acidification, which promotes cardiac damage, dysfunction or arrhythmia. In this study, we investigated the effect of ouabain on the intracellular pH (pH i ) in cultured mouse ventricular cells, using 2′,7′-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF). The average resting pH i in myocytes was 7.19. After myocytes were acid-loaded with NH 4 Cl, the pH i recovered from acidosis to the resting level within a few minutes via amiloride-sensitive Na + /H + exchange. Ouabain inhibited this pH i recovery dose-dependently with half-maximal inhibition at 3×10 −5 m , but did not suppress the ionophore monensin-induced pH i elevation. The inhibition of the pH i recovery from acidosis by ouabain is possibly caused by an inhibition of amiloride-sensitive Na + /H + exchange, which is secondary to a suppression of Na + efflux through (Na + , K + ) pump. Above results demonstrate the possibility that digitalis promotes intracellular acidosis or inhibits the pH i recovery from acidosis in ischaemic myocardium.

This study was performed to determine whether there is any difference in cation transport of red blood cells from normotensive subjects and hypertensive patients in Japan. Net Na+ efflux and net K+ influx rates were measured in sodium-loaded red cells from 19 normotensive subjects, 22 essential hypertensive patients, and 8 secondary hypertensive patients. The ratio of Na+/K+ net fluxes and the net cation flux rate were compared between these groups. The ratio of Na+/K+ net fluxes was significantly lower in essential hypertensive patients than in normotensive subjects. Parameters such as age, sex, blood pressure, plasma renin activity, and plasma aldosterone concentration were also examined in 2 groups of essential hypertensive patients, divided on the basis of their Na+/K+ net fluxes. However, there is no significant difference between the groups. These results suggest that the ratio of cation flux is related to hypertension independently of these parameters.

To determine systemic and regional hemodynamic effects of prolonged treatment with the calcium antagonist diltiazem (30 mg/kg twice daily by gastric gavage, for 3 weeks), data from 12 Wistar-Kyoto (WKY) and 10 spontaneously hypertensive (SHR) rats were compared with those obtained from 11 WKY and 10 SHR controls treated with the vehicle. Systemic and regional hemodynamics were determined in the conscious, unrestrained state using the reference sample microsphere method. Mean arterial pressure (MAP) decreased in SHR by 9% (183 +/- 4 to 167 +/- 4 mm Hg; p less than 0.05) but remained unchanged in WKY, while cardiac index (CI) tended to decrease in both strains; heart rate fell by 15% only in WKY (481 +/- 10 to 354 +/- 13 beats/min; p less than 0.05). Total peripheral resistance index (TPRI) tended to decrease in SHR but to increase in WKY. Organ blood flow in SHR decreased in skin and splanchnic organs, while organ vascular resistance decreased in brain and increased in splanchnic organs. In contrast, organ blood flow increased in heart and decreased in kidneys and skin of the WKY, while organ vascular resistance decreased in heart and increased in kidneys and skin. Thus, diltiazem produced nonuniform and different hemodynamic effects in the two strains. Further, diltiazem did not alter the cardiac mass in either rat strain. We therefore conclude that diltiazem demonstrated a mild hypotensive effect in SHR that was associated with slight reductions in CI and TPRI, the latter being nonuniformly distributed in the component organ circulations.

To clarify the mechanical adaptation and interference of coronary vessels, we studied hemodynamics of coronary circulation in control and 4 different pacing rates (80, 100, 120, 150/min) in 5 patients with angina pectoris (AP) and in 5 patients with hypertrophic cardiomyopathy (HCM). Coronary sinus flow (CSF) was measured by a Webster's thermodilution catheter, and we applied ascorbic acid-platinum reaction for the mean transit time measurement in left coronary flow (t0-t2). Coronary vascular bed (CVB) was obtained by multiplying CSF and t0-t2. CSF in AP gradually increased from 104 +/- 21 ml/min at 72/min to 148 +/- 42 ml/min at 120/min, while CSF in HCM changed slightly from 91 +/- 25 ml/min at 64/min to 94 ml/min at 120/min. Average t0-t2 in HCM was 6.0 +/- 1.6 sec in control which was significantly lower than that in AP (7.8 +/- 0.7 sec). Calculated CVB in AP increased at any given heart rate up to 120/min (13.5 +/- 2.4, 15.8 +/- 1.7, 15.0 +/- 4.7, 15.1 +/- 4.3 ml), but CVB in HCM decreased from 9.1 +/- 2.3 ml at 64/min to 8.1 +/- 1.7 ml at 120/min. These data suggest that myocardial compression and suction at different heart rates and with different cardiac muscle structures play an important role for beat to beat adjustment of coronary circulation in cardiac cycle.

To evaluate left ventricular (LV) and left atrial (LA) function in patients with borderline and established hypertension, 7 indexes of LV systolic function (cardiac index, end-diastolic volume index, ejection fraction, LV network, mean VCF, Vmax and peak dp/dt), 7 indexes of LV diastolic properties (specific compliance, LV mass index, LV wall thickness, stiffness constant, time constant T, end-diastolic pressure and peak negative dp/dt) and 3 indexes of LA function (volume index, chamber stiffness constant and muscle stiffness constant), all obtained form the data of cardiac catheterization and cineangiogram, were analyzed in patients with normotension (N, n=12), borderline hypertension (BH, n=13) and established hypertension (EH, n=17). LV systolic function was not impaired in the BH and EH groups. In the BH group, LV diastolic function was not affected, but LV wall thickness and stiffness constant were significantly greater in the EH group than in the N group. There was no significant difference in LA volume index among the 3 groups, but a significant increase of LA chamber stiffness constant was found only in the EH group as compared to the values of the N group. On the other hand, LA muscle stiffness constant was significantly greater in the BH group than in the N group, and significantly greater in the EH group than in the BH group. From these results it seemed that LV systolic and diastolic functions were not impaired in patients with borderline hypertension, and that LV systolic function was not affected, but LV diastolic function was possibly impaired in patients with established hypertension. Moreover, it was suggested that LA compliance was impaired already not only in patients with established hypertension, but also in patients with borderline hypertension.

The antianginal effects of diltiazem and nifedipine alone and in combination were evaluated in a double-blind, randomized, placebo-controlled trial in 11 patients (nine men and two women, 57 +/- 8 years old) with stable effort angina. Each patient received placebo, 30 mg of diltiazem, 10 mg of nifedipine, and 30 mg of diltiazem plus 10 mg of nifedipine four times daily for 1 week each. Antianginal efficacy was assessed by means of a treadmill exercise test. The exercise tolerance time was significantly prolonged from 235.1 +/- 52 (placebo period) to 342.2 +/- 101 sec by diltiazem (p less than .01) and to 325.6 +/- 73 sec by nifedipine (p less than .01). The drug combination further prolonged exercise time to 451.1 +/- 103 sec, which was significantly longer than the interval attained with either diltiazem (p less than .01) or nifedipine (p less than .01) alone. The plasma concentration of diltiazem was unaffected by the addition of nifedipine, whereas the plasma nifedipine concentration was significantly increased from 34.8 +/- 11 to 106.4 +/- 37 ng/ml (p less than .001) by the concomitant administration of diltiazem. These data suggest that exercise tolerance in patients with effort angina is increased by the concomitant administration of diltiazem and nifedipine associated with an increase in the nifedipine plasma concentration.

The regional and systemic hemodynamics of urapidil and prazosin were investigated after intravenous (1 mg/kg or 0.01 mg/kg, respectively) and prolonged (three weeks) oral treatment (20 mg/kg a day or 2 mg/kg a day, respectively) in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Following intravenous administration, both urapidil and prazosin decreased mean arterial pressure, mediated through a decrease in total peripheral resistance and accompanied by a transient increase in heart rate in both strains. The changes in regional circulations were more widespread after urapidil, but of longer duration after prazosin. Prolonged administration of urapidil or prazosin resulted in a significant decrease in mean arterial pressure and total peripheral resistance only in SHR. With urapidil treatment, the decrease in vascular resistance was distributed throughout all circulations, with no change in heart rate or cardiac index. Heart rate increased in WKY rats and cardiac index increased in SHR following prazosin treatment. Cardiac mass remained unchanged following treatment with either drug.

Clinical blood pressures measured at clinic by physician were higher than home blood pressures measured at home by patients in the majority of untreated patients with essential hypertension, but equivalent or lower in some patients. Clinic minus home blood pressure (delta P) were correlated with the levels of clinic blood pressure (r = 0.51, p less than 0.005 for systolic; r = 0.35, p less than 0.02 for diastolic blood pressure, respectively). The systolic delta P might be greater in the middle-aged women, especially in the fifties of females than the age-matched males (p less than 0.05). The delta P could not be altered by any antihypertensive drugs with the exception of systolic delta P with diuretic alone. The blood pressure tended to remain more stable throughout the 24-hour period in proportion as the severity of hypertension increased. The observation of circadian variation in blood pressure disclosed that the blood pressure was lower in the morning, but increased gradually, resulting in the relatively high blood pressure between the afternoon and evening in the low renin and volume expanded type of hypertension. On the contrary, the blood pressure was already high in the early morning in hypertensive patients characterized by the accelerated renin-angiotensin system and contracted volume factor.

The circadian rhythm of blood pressure in 11 patients with primary aldosteronism (ALD) and 15 patients with unilateral renovascular hypertension (RVH) was analyzed using the cosinor method which fits a cosine function to a series of data. In ALD, both systolic (SP) and diastolic blood pressures (DP) increased in the late evening ; the amplitude and acrophase of the circadian rhythm for SP were 7.3 (5.3 to 9.3, mean and 95% confidence limits) mmHg and 20 : 47 (19:42 to 21:52) hours, respectively, and for DP 2.6 (1.3 to 3.9) mmHg and 21:34 (19:40 to 23:28) hours, respectively. After excision of an adrenal adenoma in 6 patients, the circadian rhythm of SP and DP was abolished. In RVH, the acrophase of the circadian rhythm of SP and DP differed by about 12 hours ; the amplitude and acrophase for SP were 5.7 (3.9 to 7.5) mmHg and 17:49 (16:35 to 19:02) hours, respectively, and for DP 1.5(0.2 to 2.7) mmHg and 6:08 (2:44 to 9:31) hours, respectively. After various surgical interventions in 8 patients, the circadian rhythm of SP persisted with little change in acrophase, while that of DP disappeared. The difference in circadian rhythm suggests a difference in mechanisms of blood pressure control in ALD and RVH.

The effects of atriopeptin III (APIII) on systemic haemodynamics were examined in 12 anaesthetized rats. Five minutes following intravenous injection (i.v.) of 10 micrograms/kg APIII, cardiac output CO, measured by electromagnetic flowmetry, stroke volume and mean arterial pressure (MAP) decreased by 14, 13 and 8% (P less than 0.05), respectively, and total peripheral resistance (TPR) increased by 10% (P less than 0.05). Heart rate (HR) and left ventricular end-diastolic pressure (LVEDP) did not change. In order to examine cardiac performance, whole blood was infused into three groups of 12 rats each receiving either no injection, APIII (10 micrograms/kg i.v.) or APIII (10 micrograms/kg i.v.) plus a continuous infusion of phenylephrine to increase MAP to pre-injection levels. Cardiac performance curves did not differ among the three groups. These data indicate that the immediate decreases in MAP and CO produced in rats by a maximum natriuretic bolus dose of APIII were not mediated by a negative myocardial inotropic effect.

The development and reversal of tolerance to the hemodynamic and anti-anginal effects of isosorbide dinitrate in a sustained release form (ISDN-SR) were investigated in 11 male patients (mean age 58.9 y.o.) with stable effort angina. Treadmill exercise test, evaluation of hemodynamic parameters and measurement of plasma ISDN concentrations were performed during the control period, on the 1st, 7th and 14th days of therapy with 40 mg of ISDN-SR orally every 8 h and, subsequently, on the day when ISDN-SR was re-administered after a 72 h placebo period (17th day). Initially, exercise tolerance time (ETT) was prolonged significantly (p less than 0.001) by ISDN-SR from 257 +/- 50 sec in the control period to 434 +/- 55 sec on day 1. This prolongation was significantly reduced with sustained therapy and ETT was shortened to 332 +/- 69 sec on the 7th day (p less than 0.01 vs day 1) and 326 +/- 73 sec on the 14th day (p less than 0.01 vs day 1). The effects of ISDN-SR initially observed were restored after a 72 h placebo period and ETT was prolonged to 432 +/- 57 sec on the 17th day. The resting heart rate was increased significantly (p less than 0.01 vs control) and systolic blood pressure was decreased (p less than 0.001 vs control) by ISDN-SR on day 1. These changes were also diminished significantly (p less than 0.01 vs day 1) with sustained therapy and were restored after a 72 h nitrate-free interval.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was designed to investigate the effect of 4 weeks of captopril treatment on cardiac mass and performance in spontaneously hypertensive rats (SHR). Left (LV) and right (RV) ventricular mass of SHR and normotensive WKY rats was reduced (p less than 0.01). Mean arterial pressure (MAP) and total peripheral resistance index (TPRI) in the treated SHR and WKY were reduced; cardiac (CI) and stroke (SI) indices remained unaltered in SHR but increased in WKY. Ventricular performance (i.e., cardiac pumping ability), assessed by rapid blood infusion, did not differ between untreated SHR and WKY, and between treated and untreated WKY rats. However, the ventricular performance curves for the treated SHR shifted down and to the right from the untreated SHR (p less than 0.01). Moreover, when MAP of treated SHR (with regressed LV mass) was elevated to their pretreatment levels, cardiac performance curves shifted further rightward and downward. In contrast, the performance curves of treated WKY whose MAP was also elevated to the level of untreated WKY were no different from those of untreated WKY. These data demonstrate that captopril treatment (at doses used in this study) reduced MAP in SHR through decreased TPRI while decreasing biventricular mass. Furthermore, the cardiac-pumping ability of previously hypertrophied SHR hearts was reduced, suggesting that certain antihypertensive agents that diminish cardiac mass could produce impaired cardiac function when called upon to increase performance (e.g., when MAP is suddenly raised).

To evaluate the role of renal Na+K+ATPase in the presence of Goldblatt hypertension, the enzyme activity and [3H]ouabain binding were examined in cortical and medullary homogenates from two-kidney, one clip (2K1C), one-kidney, one clip (1K1C), unilaterally nephrectomized and normal rabbits. Four weeks after the surgery, systolic blood pressures (SBPs) of 2K1C and 1K1C rabbits were increased significantly to 128 +/- 3 and 129 +/- 2 mmHg, respectively. In contrast, SBPs in the normal controls and unilateral nephrectomized (1K) animals were 83 +/- 2 and 86 +/- 3 mmHg, respectively. In the 2K1C rabbits, atrophy (91%) occurred in the kidney on the ischaemic side and hypertrophy (110%) occurred in the contralateral kidney. Na+K+ATPase activity and number of [3H]ouabain binding sites were reduced in the homogenates of the ischaemic kidney of 2K1C rabbits. In the 1K1C rabbits, marked hypertrophy of the kidney (155%) occurred, and the activity of Na+K+ATPase and the number of [3H]ouabain binding sites increased slightly in the cortex and medulla, compared with the normal controls. 5'-Nucleotidase, a plasma membrane marker enzyme, remained unchanged in both groups of hypertensive rabbits. Dissociation constant (KD) values for [3H]ouabain binding did not differ significantly in the renal homogenates of of 2K1C and 1K1C, compared with findings in the normal controls. The inhibitory activity of plasma was measured by studying [3H]ouabain binding to Na+K+ATPase of renal tubular basolateral membrane vesicles purified by Percoll gradient. The inhibition was more pronounced with plasma from 2K1C, 1K1C and 1K rabbits than from the control animals. Our findings suggest that in the Goldblatt hypertensive model, changes in Na+K+ATPase activity were due to alterations in glomerular filtration rate (GFR).