Takeru Iwata

Association between elevated brain natriuretic peptide levels and the development of left ventricular hypertrophy in patients with hypertension

PURPOSE To examine whether plasma levels of brain natriuretic peptide identify hypertensive patients at risk for progressive cardiac hypertrophy. SUBJECTS AND METHODS We examined the association between plasma brain natriuretic peptide levels and left ventricular structural changes in 54 hypertensive patients and 28 normotensive control subjects. Patients were divided into those with elevated (n = 14) or normal (n = 40) levels of brain natriuretic peptide, based on a cutoff level of 41 pg/mL (2 SD above the mean in the control subjects). Left ventricular function and geometry were assessed echocardiographically at baseline and follow-up. RESULTS At baseline, initial left ventricular chamber size, wall thickness, and systolic function did not differ between the hypertensive patients and normotensive subjects. After a mean (+/- SD) follow-up of 9 +/- 3 months, blood pressure was relatively unchanged in the hypertensive patients with normal brain natriuretic peptide levels, whereas there were significant increases in systolic blood pressure and pulse pressure (both P <0.05 versus baseline) in patients with elevated brain natriuretic peptide levels. Moreover, left ventricular midwall systolic function had decreased significantly at follow-up in those with elevated levels (P <0.05 versus baseline). At follow-up, the hypertensive patients with elevated brain natriuretic peptide levels had a significantly greater left ventricular mass index and relative wall thickness than those with normal levels. Multiple regression analyses determined that only initial plasma brain natriuretic peptide was significantly (P <0.01) associated with subsequent left ventricular hypertrophy. CONCLUSION Plasma brain natriuretic peptide levels may identify hypertensive patients who are likely to have progressive cardiac hypertrophy.

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.

Paroxysmal atrial fibrillation as a cause of potentially lethal ventricular arrhythmia with myocardial ischemia in hypertrophic cardiomyopathy--a case report.

The mechanism(s) of myocardial ischemia in hypertrophic cardiomyopathy remain unclear. In this report, the authors present a 75-year-old Japanese woman with nonob structive hypertrophic cardiomyopathy in whom paroxysmal atrial fibrillation caused severe myocardial ischemia and induced sustained ventricular tachycardia. Her coronary angiogram showed normal findings, and no ischemic changes were provoked by either physical exercise testing or dobutamine stress echocardiography under sinus rhythm. In view of these findings, the rapid ventricular response in the absence of atrial contraction may aggravate or induce myocardial ischemia and predispose patients with hypertrophic cardiomyopathy to develop lethal ventricular arrhythmia.

Changes of plasma renin activity by intracerebroventricular administration of biological active peptides in conscious rats

We studied the effects of intracerebroventricular administration of angiotensin II (ANG II), bradykinin (BK), leucine-enkephalin (Leu-ENK) and neurotensin (NT) on plasma renin activity (PRA), blood pressure and heart rate in conscious and unrestrained rats. Five microliters of each peptide solution was injected into the lateral cerebral ventricle. These four peptides all produced pressor effects after intracerebroventricular injection. ANG II and NT significantly suppressed PRA, BK did not affect PRA, and Leu-ENK significantly increased PRA. The central peptidergic stimulation caused by these four peptides increased blood pressures in conscious rats but showed different effects on PRA.

Rest-redistribution thallium-201 myocardial scintigraphic study in cardiac amyloidosis

Background: Histopathological study in amyloid heart demonstrates that myocyte destructed by the extracellular deposition of amyloid protein together with viable myocyte is present. We hypothesized that rapid thallium washout may be found in amyloid heart as in regions which have a mixture of viable myocyte and scar tissue in patients with myocardial infarction. Thus, the purpose of this study was to evaluate the extent and severity of myocardial damage due to amyloid deposits using the washout rate of the tracer on rest-redistribution thallium-201 (201Tl) myocardial scans in cardiac amyloidosis patients. Methods: Rest-redistribution 201Tl myocardial scintigraphy was performed in 5 patients with biopsy-proved systemic amyloidosis with cardiac involvement (amyloidosis group). The initial and delayed images were obtained 15 min and 4 h, respectively, after intravenous injection of the tracer of 111 MBq. Washout rate of the tracer was calculated. Twelve patients with no apparent heart disease served as controls (control group). Results: Mean washout rate of the whole heart was higher in the amyloidosis group than in the control group (56 ± 9% vs 36 ± 6%, p < 0.001). Particularly, 4 of the 5 patients in the amyloidosis group presented a very high rate of thallium clearance which ranged from 57 to 61%, and died in less than a year. In the remaining 1 patient who had a normal washout rate of the tracer in the first study, it changed from 40 to 53% during the 5-year follow-up period. Conclusions: Washout rate in the setting of rest and delayed 201Tl images may represent the severity of amyloid depositions in the myocardium and may provide prognostic information.

Brain glutathione and blood pressure control.

&NA; The role of glutathione in the central nervous system in regulating blood pressure (BP) and sympathetic nerve activity (SNA) was investigated in rats. Intracerebroventricular (ICV) injection of glutathione disulfide (GSSG: 1.7‐33 nmol) resulted in a dose‐dependent increase in BP [&Dgr; mean BP: 17 ± 1 mm Hg (n = 7) for 33‐nmol dose] together with a marked increase in SNA [163 ± 13 to 672 ± 70 spikes/10 s (n = 7), p < 0.001]. Intracerebroventricular administration of its reduced form (GSH, 33 nmol) produced a vasodepressor response (&Dgr; mean BP: ‐9 ± 2 mm Hg) accompanied by a corresponding decrease in SNA [192 ± 15 to 54 ± 22 spikes/ 10 s (n = 6), p < 0.01]. These responses were not due to a leakage into the systemic circulation, since intravenous injection of GSSG or GSH (33 nmol) did not show any cardiovascular effects. Electrical stimulation of the posterior hypothalamus induced hypertension with a significant decrease of GSSG in the brain stem. The results indicate that GSSG has a stimulatory control over the sympathetic nervous system while GSH has an inhibitory effect on SNA. Glutathione disulfide and GSH may act within the central nervous system to modulate the tone of the sympathetic nervous system.

Cardiovascular effect of oral calcium supplementation : Echocardiographic study in patients with essential hypertension

Oral calcium (Ca) supplementation mildly reduces blood pressure. The authors studied the effects of Ca supplementation on the cardiovascular system in patients with mild to moderate essential hypertension. Twelve patients aged forty-nine to seventy years (7 men and 5 women, mean age with 60.3 ±7.2 years) participated. The investigators orally administered Ca (1.0 g/day for one week) under hospitalization, adding to a dietary intake of Ca (0.6 g/day). Left ventricular function and systemic arterial compliance were evaluated by M-mode and pulsed Doppler echocardiographies before and after seven days of Ca supplementation. Left ventricular contractility and afterload were not changed. Preload indicated by end-diastolic volume was significantly decreased after Ca supplementation (109.6 ±8.5 vs 107.3 ±8.2 mL, P < 0.05). Myocardial relaxation evaluated by IIa-mitral valve opening time (87.7 ±6.7 vs 82.1 ±6.2 ms, P < 0.01) and maximum descending rate of the left ventricular posterior wall (10.6 ± 1.0 vs 12.4 ±1.0 cm/s, P < 0.01), and atrioventricular net compliance assessed by the descending slope of rapid filling flow in the left ventricular inflow tract (2.63 ±0.24 vs 2.26 ±0.17 m/s2, P < 0.05), as well as systemic arterial compliance (2.05 ±0.20 vs 2.73 ±0.26 mL/mmHg, P < 0.01) were significantly improved by Ca supplementation. Oral Ca supplementation improved the disturbed left ventricular diastolic function and systemic arterial compliance.

A case of pulmonary stenosis after a repair for tetralogy of Fallot treated with percutaneous pulmonary valvuloplasty using a triple-balloon technique

The patient was a 37-year-old female who had undergone a repair for tetralogy of Fallot (TOF) at the age of 4 years. Postoperative pulmonary stenosis remained, but she continued to be managed medically. Approximately 3 years ago, at the age of 34, she exhibited a worsening of fatigue and dyspnea during exertion (New York Heart Association III), and was therefore hospitalized for a detailed examination. In cardiac catheterization, a right ventricle to pulmonary artery peak-to-peak gradient of about 90 mmHg was observed. Since it appeared that medical treatment alone would not sufficiently control her heart failure, pulmonary valvuloplasty using a triple-balloon technique was performed for the pulmonary stenosis. The peak-to-peak gradient immediately after the procedure decreased to 13 mmHg. There were no indications of restenosis approximately 6 months after the procedure, and the symptoms of heart failure in her daily life improved thereafter.

Effect of dietary NaCl on tyrosine hydroxylase in the superior cervical ganglia of Dahl rats

To investigate the involvement of peripheral catecholamines in the development of Dahl-Iwai salt-sensitive (DIS/Eis) hypertension, we performed immunohistochemical staining of tyrosine hydroxylase (TH) in the superior cervical ganglia (SCG) of DIS/Eis rats and Dahl-Iwai salt-resistant (DIR/Eis) rats, and in situ hybridization histochemistry for demonstration of TH mRNA localization in the SCG of these rats. DIS/Eis and DIR/Eis rats were fed on a high (8%) salt diet or on a low (0.3%) salt diet for 4 weeks. Nerve cells in the SCG of DIS/Eis high salt rats exhibited more intense TH-immunoreactivity (P < 0.01) and hybridization signals (P < 0.01) than those of the other experimental groups. These findings suggest that activation of peripheral sympathetic nerves may account for hypertension in DIS/Eis rats on a high salt diet.

Effects of renal denervation on renin release induced by intracerebroventricular administration of biological active peptides in conscious rats

Experiments were performed to determine whether the renal nerve mediates the renin release induced by intracerebroventricular administration of angiotensin II (ANG II), bradykinin (BK), leucine-enkephalin (Leu-ENK) and neurotensin (NT). In sham-operated rats, both ANG II and NT suppressed plasma renin activity (PRA), BK did not affect PRA, and Leu-ENK increased PRA. Renal denervation abolished the increase in PRA by Leu-ENK. Suppression of PRA by ANG II was attenuated in denervated rats. Renal denervation did not influence the renin release by BK or NT. These results suggest that the renal nerve plays an important role in elevating PRA after central stimulation by Leu-ENK. Although suppression of PRA is mainly mediated by mechanisms other than the renal nerve, the renal nerve partially participates in suppression of PRA by ANG II.