Hiromi Inariba

Significant correlation of glycated albumin, but not glycated haemoglobin, with arterial stiffening in haemodialysis patients with type 2 diabetes

Objective  We recently reported that glycated albumin (GA) is a better indicator of glycaemic control compared with glycated haemoglobin (HbA1c) in haemodialysis (HD) patients with type 2 diabetes. As poor glycaemic control is considered an independent risk factor for atherosclerosis in diabetes, the relationship between GA, HbA1c and arterial stiffening was examined in HD patients with type 2 diabetes.

Intracellular pH in platelets from spontaneously hypertensive rats and Wistar-Kyoto rats

Intracellular pH in platelets from spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY) was measured using a pH-sensitive fluorescent dye, 2‘,7’-bis(carboxyethyl)carboxyfluorescein tetraacetoxy methyl ester (BCECF). Intracellular pH in platelets was significantly higher in SHR than in WKY (7.12 ± 0.04 versus 7.06 ± 0.02, P < 0.01; n = 10). There was a close correlation between intracellular pH and systolic blood pressure (r = 0.66, P < 0.01). Addition to platelets of 1-(5-isoquinolinesulphonyl)-2-methylpiperazine (H-7), a specific inhibitor of protein kinase C, produced a significantly larger decrease in intracellular pH in SHR than in WKY (0.06 ± 0.02 versus 0.03 ± 0.00, P < 0.01, n = 5). These results suggest that protein kinase C may play an important role in the increased intracellular pH in SHR.

Increased Na+/H+ exchange activity in vascular smooth muscle cells of spontaneously hypertensive rats and possible involvement of protein kinase C

1. Na+ influx into cultured vascular smooth muscle cells (VSMC) obtained from spontaneously hypertensive rats (SHR) and from Wistar‐Kyoto rats (WKY) was measured. Na+ influx via the Na+/H+ exchange system was measured as the rate of 22Na+ influx into cultured VSMC sensitive to ethylisopropylamiloride (EIPA), a specific inhibitor of the exchange system.

Chronic Antihypertensive Drug Treatment Decreases Protein Kinase C Activity in Platelets from SHR

There is evidence that protein kinase C activity in platelets from adult SHR is significantly higher than this activity in age-matched WKY. In the present study, protein kinase C activity in the SHR was measured following antihypertensive drug treatment. Chronic administration of enalapril to SHR for 2 weeks decreased both systolic blood pressure and protein kinase C activity to the levels seen in the WKY. Similar results were obtained in case of chronic treatment of SHR with hydralazine or nifedipine. These results suggest that enhanced protein kinase C activity of SHR can be suppressed by lowering blood pressure by antihypertensive drugs.

Expression of c-myc proto-oncogene in hearts and cultured smooth muscle cells of spontaneously hypertensive rats

We studied the expression of c-myc proto-oncogene in hearts and cultured aortic smooth muscle cells of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY), in order to investigate the association of the c-myc gene with cardiac hypertrophy and atherosclerosis in SHR. Transcription of the c-myc gene in hearts of SHR was higher than that of WKY at 10 weeks of age, when cardiac hypertrophy had developed in SHR. The c-myc gene expression in cultured aortic smooth muscle cells of SHR, after the addition of serum to the serum-deprived cultures, was higher than that of WKY. These results suggest that the enhanced expression of the c-myc gene in the hearts and cultured aortic smooth muscle cells of SHR may be associated with the growth control of these cells, and may play a role in the development of cardiac hypertrophy and atherosclerotic lesions in SHR.

Angiotensin II induced biphasic inositol 1,4,5-triphosphate response in rat vascular smooth muscle cells.

We examined angiotensin II induced changes of inositol 1,4,5-triphosphate (Ins(1,4,5)P3) in cultured vascular smooth muscle cells from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) using a specific protein binding assay system. We observed a rapid biphasic Ins(1,4,5)P3 response, which peaked at 5 s and at 30 s after angiotensin II stimulation. At every period of time the Ins(1,4,5)P3 level of SHR was 2- to 5-fold higher than that of WKY. Thus, the Ins(1,4,5)P3 specific assay revealed a complex Ins(1,4,5)P3 response after angiotensin II stimulation and suggested the need for further investigation of the Ins(1,4,5)P3 metabolism following agonist stimulation in vascular smooth muscle cells.

Pharmacokinetics and effects of cilazapril in hypertensive patients on hemodialysis.

高血圧を伴う維持血液透析患者7例に長時間作用型アンジオテンシン転換酵素 (ACE) 阻害薬, cilazaprilを投与し, その効果と体内動態について検討した. 透析日, 非透析日それぞれにcilazapril, 0.5mgを単回投与し血圧, cilazaprilおよびその代謝活性体cilazaprilatの血中濃度, 血清ACE活性, 血漿レニン活性, アンジオテンシンI, II (AI, AII) 濃度を測定した。 血圧はcilazaprilの投与により透析日, 非透析日ともに有意に低下した. Cilazaprilの代謝活性体, cilazaprilatの最高血中濃度 (Cmax), 最高血中濃度到達時間 (Tmax) は非透析日では21.4±4.1ng/ml, 18.3±2.7hであり, 透析日では14.0±4.7ng/ml, 11.2±3.4hであった. Cilazaprilatの半減期は28.6hと排泄の遅延が著明であるが, 透析中の半減期は3.4hと短縮していた. 上記の薬行力学的パラメータを用いて, cilazapril, 0.5mgを-週間反復投与し, 2日に-度透析を行った場合を想定して求めたシミュレーションではcilazaprilatの有効血中濃度は保たれ, 過度の蓄積はみられないと予測された. したがって透析患者にcilazaprilを投与する際は, 0.5mgを一日一回投与することが適当と考えられる. 血清ACE活性は薬剤投与後, 6時間より24時間にわたって80%以上抑制された. しかし, 血漿レニン活性, 血漿AI, AII濃度にはcilazapril, 0.5mg単回投与では有意な変化はみられず, cilazaprilの降圧効果は血中のレニン・アンジオテンシン系よりもむしろ組織のレニン・アンジオテンシン系を抑制することによる可能性が示唆された.

Corticosteroid- and Furosemide-Induced Increase in Proteinuria in Nephrosis

A corticosteroid- and furosemide-induced excessive increase in proteinuria developed in a 34-year-old nephrotic patient with focal glomerulosclerosis. The concentration of urinary protein increased almost in parallel with that of urinary glucose. This finding indicates that corticosteroids and/or furosemide can promote the disturbance of the tubular reabsorption mechanism together with increases in glomerular permeability and glomerular filtration rate.

Angiotensin Converting Enzyme Activity in Brain Microvessels of Rats

Angiotensin converting enzyme (ACE) is a carboxyl terminal dipeptidyl dipeptidase, which is known to convert angiotensin I to angiotensin II (Ang II) and to hydrolyze bradykinin and enkephalin. In the brain, ACE is located in endothelial cells of capillaries throughout the brain, in the subfornical organ, and in the brush border of choroidal epithelial cells in contact with cerebrospinal fluid [1]. Administration of Ang II into the brain ventricles induces thirst [2], a rise in arterial blood pressure, and secretion of vasopressin [3]. Recently, the specific binding of Ang II to the membrane fraction of canine brain microvessels was detected, suggesting the role of Ang II in regulation of the brain microcirculation and transport across the blood-brain barrier [4]. Since ACE in the brain microvessels might affect the brain microcirculation by modulating the local production of Ang II, we measured ACE activity in brain microvessels obtained from 13-week-old spontaneously hypertensive rats (SHR), Wistar-Kyoto rats, and SHR of the same age under antihypertensive therapy to clarify the effect of hypertension on the brain microvessels.