Seijiro Shimada

Significant role of the increase in renin-angiotensin system in cardiac hypertrophy and renal glomerular sclerosis in double transgenic tsukuba hypertensive mice carrying both human renin and angiotensinogen genes.

Tsukuba hypertensive mice (THM) are a hypertensive model prepared by mating a transgenic mice with human renin gene and a transgenic mice with human angiotensinogen gene. In the present study, we examined effects of renin-angiotensin system (RAS) on cardiac hypertrophy and renal disorders using Tsukuba hypertensive mice. While THM showed an increase of about 30 mmHg in systolic pressure compared to C57BL/6 mice employed as normal control animals, the increase in blood pressure was not observed in the mice to which either gene was transferred. Urinary volume, water intake volume, urinary albumin excretion, heart to body weight ratio and renal glomerular sclerosis index increased significantly in THM, but none of these parameters showed a significant difference from the C57 mice when they were examined in mice to which either of the genes was transferred. In contrast, when lisinopril was administered to THM, all the parameters decreased significantly without lowering the systolic pressure. From these findings, it was demonstrated that RAS was playing a significant role in cardiac hypertrophy and renal disorders of THM and that lisinopril had inhibitory effects on cardiac hypertrophy and renal glomerular sclerosis by inhibiting RAS.

Renin-angiotensin system stimulates cardiac and renal disorders in Tsukuba hypertensive mice.

1. The role of the renin–angiotensin system (RAS) in cardiac hypertrophy and nephropathy was examined in Tsukuba hypertensive mice (THM) carrying both human renin and angiotensinogen genes.

EFFECT OF AN ANGIOTENSIN II RECEPTOR ANTAGONIST, TCV‐116, ON NEOINTIMAL FORMATION FOLLOWING BALLOON INJURY IN THE SHR CAROTID ARTERY

1. In the present study, we examined the effect of a novel angiotensin II type I receptor antagonist, TCV‐116, on carotid neointimal formation after balloon injury in SHR and WKY rats.

α1-Adrenergic Stimulation Induced Hypertrophy in Protein Kinase C Down-Regulated Cultured Cardiac Myocytes

To examine whether protein kinase C (PKC) activation is essential for the induction of cardiac myocyte hypertrophy caused by alpha1-adrenergic stimulation, we investigated the hypertrophic effect of phenylephrine in PKC down-regulated and non-treated cultured cardiac myocytes obtained from neonatal Sprague-Dawley rat ventricles. The treatment with 10 nmol/L 12-tetra decanoylphorbol-13-acetate (TPA) for more than 2 hours decreased PKC activity by approximately 80% without marked hypertrophy. Phenylephrine increased [14C] phenylalanine (Phe) incorporation in both TPA non-treated and treated cells, 1.54- and 1.71-fold as large as control, respectively. The cell surface area also enlarged in both groups, 1.67- and 1.74-fold, respectively. Thus, phenylephrine induced the similar grade hypertrophy in cultured cardiac myocytes even when PKC was down-regulated. These results suggest that conventional PKC activation may not be essential for mediating myocyte hypertrophy by alpha1-adrenergic stimulation.

Analyzing the association between aortic regurgitation and atherosclerosis: is pulse pressure a cause of atherosclerosis?

ABSTRACT If pulse pressure, one of the mechanical stresses, is a risk factor for atherosclerotic cardiovascular disease, then atherosclerosis should be progressive in aortic regurgitation which is a representative disease with increased pulse pressure. This cross-sectional study included 1,149 patients. We examined the influence of aortic regurgitation on maximum intima-media thickness or brachial-ankle pulse wave velocity. The degree of aortic regurgitation was classified into 4 grades by color Doppler examination. There were 177 patients with aortic regurgitation. Pulse pressure was significantly higher in patients with aortic regurgitation than in those without it. On multiple regression analysis, aortic regurgitation was not found to be a significant independent variable for maximum intima-media thickness [standard partial regression coefficient: aortic regurgitation = grade 1, 0.011, P = 0.7635; aortic regurgitation ≥ grade 2, −0.034, P = 0.3289] and brachial-ankle pulse wave velocity [standard partial regression coefficient: aortic regurgitation = grade1, −0.043, P = 0.1197; aortic regurgitation ≥ grade2, 0.002, P = 0.9358] after adjusting for age, sex, body mass index, presence or absence of cardiovascular disease, antihypertensive treatment, diabetes, dyslipidemia, and smoking. These results found no causal association between aortic regurgitation and atherosclerosis, and were a contradiction to the opinion that pulse pressure was a risk factor of atherosclerosis.

Unusual Case of Cardiac Amyloidosis Preceded by a Twenty-year History of Dilated Cardiomyopathy and Heart Failure

Amyloidosis is a well-known but uncommon disease, and the physician must maintain a high index of suspicion in order to make a timely diagnosis. The expected survival of patients with cardiac amyloidosis is generally poor. In particular, survival has been reported to be 4-12 months for patients with amyloid light-chain amyloidosis with congestive heart failure. We herein report a rare case of cardiac amyloidosis in which the patient presented with cardiac hypertrophy after a 20-year history of dilated cardiomyopathy and heart failure.

Effect of lisinopril on deposition of iron in renal tissue in Tsukuba hypertensive mice carrying human renin‐angiotensin system genes

Tsukuba hypertensive mice (THM) are transgenic mice that carry both human renin and angiotensinogen genes and overexpress the human renin‐angiotensin system (RAS). In the present study, the effect of lisinopril on deposition of macromolecular iron in renal tissue in THM was evaluated. Twelve‐week‐old male THM were divided into the following groups: lisinopril dosage group (ACEI group), hydralazine dosage group (hydralazine group), and a no‐drug group (control group). Age‐matched male C57BL/6 mice (wild group) were used as normal controls. Each mouse was treated with a drug for 8 weeks. All mice were euthanised at 20 weeks of age, and their kidneys were fixed and stained with Berlin‐blue. Systolic blood pressure was significantly higher in the control group than in the wild group, and it decreased significantly to similar levels in the ACEI group and the hydralazine group. Iron deposition was observed in proximal renal tubules in the control group and the hydralazine group, but iron deposition was not observed in the ACEI group or the wild group. The results of the study suggest that the RAS plays an important role in the deposition of iron in the proximal renal tubules in THM, and that lisinopril prevents this deposition.