Biomedical subjects
K Hiwada
Publications and source records attributed to K Hiwada.
Quantitative measurement of extra-renal renin mRNA by polymerase chain reaction.
We established a simplified method of the quantitative measurement of extra-renal renin messenger RNA using polymerase chain reaction system. We could detect the renin messenger RNA in the kidney, heart, aorta and adrenal gland from a single RNA sample obtained from a Wistar-Kyoto rat. In the kidney, heart, aorta and adrenal gland, the contents of renin messenger RNA were found to be 55.8 +/- 17.8, 0.15 +/- 0.05, 0.11 +/- 0.03 and 0.16 +/- 0.07 pg/micrograms of total RNA (n = 5, mean +/- s.d.), respectively. The present method is very useful to study the extra-renal renin-angiotensin system.
Effect of disopyramide on systolic and early diastolic time intervals in patients with hypertrophic cardiomyopathy.
The present study clarified the effect of disopyramide on left-ventricular function in patients with hypertrophic cardiomyopathy (5 obstructive type: HOCM, 21 non-obstructive type: HNCM). The systolic and early diastolic time intervals were assessed 3 hours after a single oral administration of 100-mg disopyramide. The following parameters were evaluated at rest and after administration of disopyramide: 1) left-ventricular ejection time index (LVETI), 2) pre-ejection period index (PEPI), 3) the interval from aortic component of the second heart sound to mitral valve opening (IIA-MVO), and 4) the interval from MVO to O point of apexcardiogram (MVO-O). LVETI in HNCM did not change after disopyramide but that in HOCM was significantly shortened (P less than .05). PEPI in both HOCM and HNCM was significantly prolonged after administration of disopyramide. IIA-MVO time in both HOCM and HNCM was not influenced by disopyramide. MVO-O time in both HOCM and HNCM was significantly shortened after disopyramide. These results suggest that 1) shortening of LVETI in HOCM after disopyramide seemed to be due to the decrease in pressure gradient, 2) PEPI prolongation after disopyramide reflected the decrease in myocardial contractility, and 3) shortening of MVO-O time after disopyramide indicated the improvement of left-ventricular filling. The authors conclude that disopyramide may be an important new therapeutic agent in the treatment of patients with hypertrophic cardiomyopathy.
Kidney renin gene expression after renin inhibition in the marmoset.
1. The effects of renin inhibitor ES-8891 on renin synthesis and its secretion by the kidney were investigated in normotensive sodium-depleted marmosets. We measured plasma renin activity, plasma immunoreactive renin concentration, plasma angiotensin II concentration and kidney renin mRNA content after oral administration of ES-8891 (60 mg day-1 kg-1) for 1 week. 2. The mean blood pressure was significantly decreased (P less than 0.01) on day 7 after oral administration of ES-8891. There was no significant change in heart rate during the administration. 3. Oral administration of ES-8891 for 1 week markedly decreased the plasma renin activity, the plasma immunoreactive renin concentration and the plasma angiotensin II concentration (to 18%, 41% and 24% of the corresponding control values; P less than 0.05 for each, n = 5). 4. The kidney renin mRNA content in ES-8891-treated marmosets was significantly lower than that in normal controls (4.2 +/- 3.5 versus 12.8 +/- 5.5 pg/micrograms of total RNA, means +/- SD, P less than 0.05, n = 5). 5. Oral administration of the renin inhibitor ES-8891 for 1 week not only inhibited plasma renin activity but also decreased renin synthesis and its secretion by the kidney.
Serum creatine kinase MM isoforms in hypertrophic cardiomyopathy.
1. To determine whether a persistent release of creatine kinase from the myocardium occurs in patients with hypertrophic cardiomyopathy, the activities of serum creatine kinase MM isoforms were measured in 22 patients with hypertrophic cardiomyopathy and in 14 normal control subjects. 2. Serum creatine kinase MB activity was significantly higher in patients with hypertrophic cardiomyopathy (7.8 +/- 3.8 i.u./l) than in normal control subjects (0.4 +/- 0.8 i.u./l; P less than 0.01). 3. Serum MMa, MMb and MMc activities in patients with hypertrophic cardiomyopathy were 19.4 +/- 4.1%, 26.7 +/- 2.5% and 33.5 +/- 7.0% of the total creatine kinase MM activity, respectively. These values for each isoform were significantly different from those in normal control subjects (11.3 +/- 3.0%, 21.5 +/- 4.4% and 40.7 +/- 7.0%, respectively). The MMa/MMc activity ratio was significantly higher in patients with hypertrophic cardiomyopathy (0.61 +/- 0.25) than in normal control subjects (0.30 +/- 0.10; P less than 0.01). 4. Our results indicate that a small amount of the myocardial tissue isoform of creatine kinase MM (MMa) is constantly released in many patients with hypertrophic cardiomyopathy.
Scintigraphic assessment of cardiac adrenergic innervation in patients with essential hypertension.
To assess the regional cardiac adrenergic innervation in patients with essential hypertension (EHT), simultaneous iodine-123 metaiodobenzylguanidine ([123I]MIBG) and thallium-201 (201Tl) myocardial imagings were performed in five patients with EHT, seven patients with hypertrophic cardiomyopathy (HCM), and seven normal subjects. Short axial images at rest were divided into five segments: anterior, septal, posterior, lateral, and apical segments. Percent regional uptake (%RU) of 201Tl except the septal segment in patients with EHT showed no significant difference. However, the %RU of [123I]MIBG at posterior, lateral, and apical segments was significantly lower than that at anterior and septal segments in EHT. This intraimage heterogeneity of [123I]MIBG was also observed in HCM. These results suggest that there is a difference in regional adrenergic innervation of the left ventricle with myocardial hypertrophy.
Characteristics of systolic time intervals in patients with pheochromocytoma.
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.
[A senile patient with Rendu-Osler-Weber disease who underwent resection of 4 multiple bilateral pulmonary arteriovenous fistulas].
A 70-year-old female patient with multiple bilateral pulmonary arteriovenous fistulas was referred to our hospital for its treatment. She had experienced frequent epistaxis and had nasopharyngeal telangiectasia. Her mother, sister and all four children also suffered from epistaxis. We diagnosed this patient as Rendu-Osler-Weber disease combined with multiple bilateral pulmonary arteriovenous fistulas. Her chest roentgenogram revealed 4 arteriovenous fistulas in the left lung and 2 arteriovenous fistulas in the right. On admission arterial blood gas analysis while breathing room air showed a PaO2 of 39.8 torr and an SaO2 of 75.4%. The percent of R-L shunt was calculated to be 56.5%. Because of severe hypoxemia, she underwent resection of four large fistulas in segments 3, 4, 5, and 8 of the left lung. Twenty-eight days after the operation, the PaO2 was 76.4 torr and SaO2 was 95.7%. There was no sign of enlargement in size of the remaining arteriovenous fistulas.
Effect of renin inhibitor, ES-8891, on renal renin secretion and storage in the marmoset: comparison with captopril.
We investigated the effects of the human renin inhibitor, ES-8891, and captopril on renal renin secretion and storage in the marmoset. Either ES-8891 (30 mg/kg) or captopril (2 mg/kg) was given orally twice a day for 1 week to conscious, sodium-depleted marmosets (n = 6 for each group). The ES-8891-treated group displayed a significant reduction in mean arterial pressure (MAP), plasma renin activity (PRA) and plasma immunoreactive renin (PIR) compared with the control group. Kidney renin content was significantly increased compared with the control group and enlarged renin granules containing heterogenous internum were observed in juxtaglomerular cells after treatment with ES-8891. Treatment with captopril significantly increased PRA and PIR compared with the control day as well as increasing kidney renin content and the number of renin granules with crystalline content in juxtaglomerular cells compared with the control group. These results suggest that ES-8891 inhibits both PRA and renin secretion from the kidney, resulting in an increase in renal renin storage.
Blood pressure and heart rate variability in elderly patients with isolated systolic hypertension.
To investigate the circadian profiles of BP and heart rate in elderly patients with isolated systolic hypertension (ISH), the variability of BP and heart rate during day time (daytime) and the amplitudes of nocturnal fall were evaluated in ISH (n = 19) comparing with those of essential hypertensive patients (EHT, n = 18) and normotensive subjects (NT, n = 16) in the same age range. ISH showed a significantly wider BP variability during the day time and a greater amplitude of nocturnal fall compared with EHT and NT. However, the heart rate variability during the daytime and the amplitude of nocturnal fall were similar among the three groups. ISH showed a stronger correlation between BP and heart rate during 24 hours compared with EHT and NT. Approximately 80% of ISH showed a significant positive correlation between BP and heart rate. These results suggest that the BP of ISH patients is susceptible to fluctuations in autonomic nerve activity.
[A case of neurofibromatosis 2 combined with a vagal neurilemmoma in the mediastinum].
A 39-year-old man was referred to our hospital for further evaluation of an abnormal mediastinal shadow on chest X-ray film. CT scan of the chest showed a cyst-like tumor in the mediastinum. CT scan of the brain to investigate the impairment of hearing revealed bilateral cerebropontine angle tumors. Histological examination of both tumors revealed neurilemmoma. Neurofibromatosis 2 combined with a vagal neurilemmoma in the mediastinum is very rare.
Effect of renal denervation on the development of hypertension in Dahl-Iwai salt-sensitive rats.
Renal denervation has been shown to delay the onset of hypertension in spontaneously hypertensive rats and DOCA-salt sensitive rats. We investigated the contribution of the renal nerves to the development of hypertension in Dahl-Iwai salt-sensitive (DS) rats. Bilateral renal denervation or sham-operation was carried out in DS rats, and animals were then kept on a high salt diet (study I) or on a normal salt diet (study II). DS rats became severely hypertensive (207 +/- 8 mmHg) after 4 weeks on a high salt diet. They became mildly hypertensive (156 +/- 3 mmHg) after 4 weeks on a normal salt diet. In both studies, renal denervation exerted no effect on the development of hypertension in the DS rats. The urinary sodium excretion, urinary volume, heart rate and body weight were unaltered by renal denervation. These results indicate that the renal nerves do not make a major contribution to the development of hypertension in DS rats.
[Beneficial effect of diltiazem on pulmonary hypertension in a patient with Hughes-Stovin's syndrome].
A 54 year-old female who had a history of hemoptysis was admitted to our hospital because of dyspnea on effort. Pulmonary arterial pressure was elevated and pulmonary arteriography showed multiple pulmonary arterial aneurysms and occlusion of the left upper lobe pulmonary artery. Systolic pulmonary arterial pressure was 110 mmHg when measured by continuous wave Doppler echocardiography. From the clinical and angiographical findings, we diagnosed this patient as having Hughes-Stovin's syndrome (forme fruste). 30 mg of diltiazem per day was initially used, and 80 mg was used thereafter. After 2 months follow up of the medication with diltiazem, systolic pulmonary arterial pressure decreased from 110 mmHg to 61 mmHg and clinical symptoms improved dramatically.
Influence of age and severity of hypertension on blood pressure response to isometric handgrip exercise.
The influence of age and severity of hypertension on the blood pressure response to isometric handgrip exercise (IHG) was studied in essential hypertensive patients (n = 122). The change in blood pressure during IHG in elderly patients with isolated systolic hypertension (ISH) (n = 12) was also studied. Left ventricular hypertrophy due to hypertension was used as an index of the severity of hypertension. The change in systolic blood pressure (SBP) during IHG was markedly greater in essential hypertensives than in normotensive subjects (n = 36). Among hypertensive patients, the change in SBP increased with increasing severity of hypertension. This change in SBP was not influenced by age. The change in SBP during IHG in patients with ISH was significantly smaller than that in essential hypertensive patients and was similar to that in normotensive subjects in the elderly. These results demonstrate that age does not affect the increased blood pressure response to IHG in essential hypertensive patients but the greater the severity of hypertension, the greater the increase in SBP during IHG. Elderly patients with ISH do not have an enhanced blood pressure response to IHG.
Plasma atrial natriuretic factor in isolated systolic hypertension in the elderly: response to hypertonic saline infusion.
Plasma immunoreactive atrial natriuretic factor (ANF) and urinary sodium excretion were measured in elderly patients with isolated systolic hypertension (ISH) (n = 11), age-matched essential hypertensive patients (EHT; n = 16) and normotensive subjects (NT; n = 9) before and during a 60 min infusion of hypertonic saline (120 mEq of Na+). An exaggerated natriuresis during the sodium load was observed only in ISH. Baseline plasma ANF levels in ISH were significantly lower (P less than 0.05) than those of EHT and NT. There was no significant change in plasma ANF in EHT and NT subjects after the saline load. In contrast, there was a significant increase in plasma ANF (P less than 0.05) after the saline load in ISH. The change in urinary sodium excretion was significantly correlated with the change in plasma ANF (r = 0.75, P less than 0.01) in ISH. We conclude that an exaggerated natriuresis during a hypertonic saline infusion may be linked to an increase in plasma ANF in elderly ISH patients.
Co-localization of immunoreactive forms of calponin with actin cytoskeleton in platelets, fibroblasts, and vascular smooth muscle.
Calponin is an actin binding protein found in the smooth muscle cells of chicken gizzard. The localization of the protein was examined in bovine platelets, mouse fibroblasts, and the smooth muscle cells of the bovine aorta. Immunoblotting of whole platelet lysates revealed that the antibody to chicken gizzard calponin recognized two proteins with apparent molecular masses of 37 and 23 kDa in the resting state and an additional high-molecular-weight component (approximately 40 kDa) in the activated state. The localizations of calponin and caldesmon, and the correlation of their localizations with that of the actin cytoskeleton were analyzed by immunofluorescence microscopy using appropriate antibodies and rhodamine-phalloidin. In resting bovine platelets, calponin exhibited the same distribution as actin filaments, which are organized in a characteristic wheel-like structure. A similar distribution was observed with the anti-caldesmon antibody. Colocalization of calponin and actin were shown in activated platelets and along stress fibers of both fibroblasts and smooth muscle cells. These results suggest not only a cytoskeletal role associated with microfilaments but also a regulatory role of these proteins for actin-myosin interaction.
Gene cloning and nucleotide sequence of SM22 alpha from the chicken gizzard smooth muscle.
A full length of cDNA encoding SM22 alpha from chicken gizzard smooth muscle was cloned and sequenced. Cloned cDNA had a total length of 1214bp and contained a single open reading frame which encodes 200 amino acids with a calculated molecular weight 22214. The predicted amino acid sequence was in complete agreement with the sequence determined by Pearlstone et al. using Edman degradation method (J. Biol. Chem. 262:5985, 1987) except for two additional residues, isoleucine and serine at the C-terminus.
[Mycotic aneurysm of the sinus of Valsalva and complete atrioventricular block complicating infectious endocarditis with aortic regurgitation: a case report].
A patient with a mycotic aneurysm of the sinus of Valsalva and heart block secondary to infectious endocarditis was described. This 46-year-old man was admitted to our hospital on May 9, 1990, because of fever and progressive general malaise after extraction of a tooth. Physical examination on admission revealed blood pressure of 98/62 mmHg, pulse rate 96 per min, temperature 37.7 degrees C and respiration 35 per min. Auscultation of the heart revealed a grade 3/6 systolic murmur and a grade 2/6 diastolic murmur at the third left intercostal space. Chest radiograph showed mild cardiomegaly with moderate lung congestion. Electrocardiography revealed the first grade atrioventricular block. Echocardiography demonstrated vegetations on the aortic valve, and perforation of the non-coronary sinus of Valsalva. The prolapsed non-coronary sinus of Valsalva extended into the right atrium. Doppler echocardiography revealed a severe aortic regurgitant jet in the diastolic phase. We diagnosed the patient as having aortic regurgitation with a mycotic aneurysm of the non-coronary sinus of Valsalva due to infectious endocarditis. His condition remained severely ill despite intensive medical treatment. On May 14, 1990, aortic valve replacement and excision of the mycotic aneurysm were performed. The commissural portions of the aortic cusps were heavily thickened and calcified. The mycotic aneurysm was very fragile. During manipulating the mycotic aneurysm, the sinus accidentally perforated into the right atrium. The cardioaortic fistula was closed with a goretex patch. A demand pacemaker was implanted because of postoperative complete atrioventricular block.(ABSTRACT TRUNCATED AT 250 WORDS)