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K Kamide

Publications and source records attributed to K Kamide.

At least 19 recordsLinked to original sources
PubMed2000

Deletion polymorphism of angiotensin-converting enzyme gene is associated with postprandial hyperglycaemia in individuals undergoing general check-up.

1. Deletion polymorphism, DD, of the angiotensin-converting enzyme (ACE) gene is reported to be related to cardiovascular disease, which is frequently based on insulin resistance. 2. To clarify the relationship between the ACE genotype DD and plasma glucose increases after an oral glucose load, we performed 75 g oral glucose tolerance test (OGTT) in 301 nondiabetic men (age range 30-60 years) undergoing general check-up. 3. Insertion/deletion (I/D) polymorphism of the ACE gene was explored using a polymerase chain reaction. The frequency of the II, ID and DD genotypes was 0.43, 0.43 and 0.14, respectively. 4. There were no differences in baseline clinical characteristics between subjects with each ACE genotype. 5. The mean (+/- SEM) plasma glucose level at 60 min of the OGTT was significantly higher in subjects with the DD genotype (170.8 +/- 6.9 mg/dL) than in subjects with either the II or ID genotype (mean value for two groups 156.6 +/- 2.7 mg/dL; P < 0.05). Moreover, the mean percentage change of plasma glucose after 60 min of the OGTT, a marker of plasma glucose increase, was significantly higher in individuals with the DD genotype than in individuals with either the II or ID genotypes. 6. In contrast, the mean fasting plasma glucose level, the plasma glucose level at 120 min, the glucose response area and the fasting insulin level were not different between individuals with the DD genotype and individuals with other genotypes. 7. In conclusion, subjects with the DD genotype showed transiently higher levels of plasma glucose after an oral glucose load than subjects with other genotypes. Further studies are required to determine whether the association between ACE genotype and postprandial hyperglycaemia influences the incidence of cardiovascular disease and diabetes mellitus.

Adult↗
PubMed2000

Insulin and insulin-like growth factor-I promotes angiotensinogen production and growth in vascular smooth muscle cells.

BACKGROUND: Circulating insulin and insulin-like growth factor-I (IGF-I) levels are increased in patients with hypertension and insulin resistance. Since both hormones are known to have cell growth-promoting effects, they may contribute to the progression of vascular hypertrophy in patients with insulin resistance. Insulin-mediated activation of the vascular renin-angiotensin system (RAS) stimulates growth in cultured rat vascular smooth muscle cells (VSMC). OBJECTIVE: In order to evaluate the role of IGF-I-mediated activation of components of the tissue RAS, we examined the effect of IGF-I receptor stimulation on cell proliferation, and production of angiotensinogen in cultured VSMC. STUDY DESIGN: Aortic VSMC were derived from male Sprague-Dawley rats. IGF-I and insulin-mediated DNA synthesis were estimated by 3H-thymidine uptake (3H-TdR) with or without the angiotensin I converting enzyme inhibitor, captopril. Moreover, angiotensinogen released by the cells to the culture medium was determined by radioimmunoassay with or without the anti-IGF-I receptor antibody alphaIR3 or captopril. RESULTS: Both IGF-I and insulin increased 3H-TdR uptake by cultured rat VSMC (P < 0.05). Captopril blocked IGF-I and insulin-mediated 3H-TdR uptake (-34.4 +/- 1.9% and -32.7 +/- 1.8%, P < 0.05, respectively). IGF-I increased the angiotensinogen level in the medium by 30.6 +/- 2.9% (P < 0.01). Insulin also stimulated angiotensinogen synthesis by 26.3 +/- 2.2% (P < 0.01). Captopril and alphaIR3 significantly suppressed angiotensinogen production stimulated by both IGF-I and insulin. CONCLUSIONS: These results indicate that IGF-I as well as insulin stimulates angiotensinogen production and growth in VSMC. Thus, both hormones may independently play a role in progression of the vascular hypertrophy and atherosclerosis in patients with hypertension and insulin resistance through activation of the tissue RAS.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

[Insulin].

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Humans↗
PubMed1999

Characterization of liposomes carrying von Willebrand factor-binding domain of platelet glycoprotein Ibalpha: a potential substitute for platelet transfusion.

Platelet glycoprotein (GP) Ib/IX/V complex is a receptor for von Willebrand factor (vWf), which plays a crucial role in primary hemostasis by mediating platelet adhesion to injured blood vessels. We have expressed in CHO cells a fragment of GPIba that retained a vWf-binding function. The recombinant fragment (rGPIba) was incorporated into liposomes and evaluated their functions in vitro. rGPIba on the liposome surface was detectable by flow cytometric analysis. Addition of vWf and ristocetin caused specific agglutination of rGPIbalpha-liposomes, as evaluated by an aggregometer or a fluorescent microscopy. When ristocetin was added to platelet-rich plasma (PRP) pre-mixed with rhodamine-labeled rGPIbalpha-liposomes, platelets aggregated and rhodamine-fluorescence was strongly positive in the platelet thrombi, suggesting that heterologous aggregation (attachment of liposomes to platelets) occurred. Platelet aggregation in PRP at low platelet concentration (20-80 x 10(6)/ml) was enhanced by rGPIbalpha-liposomes in a dose-dependent manner. Thus, rGPIbalpha-liposomes may accumulate on vWf-exposed subendothelial tissues and enhance platelet function in vivo, supporting hemostasis in thrombocytopenic individuals.

Animals↗
PubMed1998

Insulin-mediated growth in aortic smooth muscle and the vascular renin-angiotensin system.

Insulin has been shown to directly affect blood vessel tone and to promote vascular hypertrophy, but the mechanism of these actions remains uncertain. Because angiotensin I (Ang I)-converting enzyme inhibitors have been shown to improve insulin action and to impede the progression of vascular hypertrophy in hypertensive animal models, it is possible that the vascular properties of insulin may be mediated through the tissue renin-angiotensin system (RAS). To evaluate this relationship, we first investigated the effect of insulin on components of the RAS using cultured rat vascular smooth muscle cells (VSMCs). Insulin treatment (1000 microU/mL) markedly increased angiotensinogen mRNA expression and angiotensinogen production. We next investigated the role of the RAS in insulin-mediated cell proliferation, using [3H]thymidine uptake. Studies were done both with insulin alone and in the presence of captopril (1x10(-7) to 10(-5) mol/L) and losartan (1x10(-9) to 10(-7) mol/L). [3H]Thymidine uptake was increased significantly by 1000 microU/mL insulin, and this stimulation was reduced by 1x10(-6) mol/L captopril (-38.8%, P<0.05) and by 1x10(-8) mol/L losartan (-37. 5%, P<0.05). Further studies showed that the degree of insulin-mediated [3H]thymidine uptake in VSMCs could be duplicated by 4x10(-10) mol/L Ang II. Losartan reduced the effects of both Ang II and insulin on [3H]thymidine uptake by about 40% to 45% of baseline (P<0.05). Captopril reduced insulin-mediated [3H]thymidine uptake but did not affect Ang II-mediated [3H]thymidine uptake. In summary, insulin induced significant stimulation of angiotensinogen expression and production and stimulated growth similar to that seen with Ang II in cultured rat VSMCs. Inhibition of Ang II production or its binding to the Ang II type 1 (AT1) receptor inhibited insulin-mediated growth in a fashion similar to that seen with inhibition of Ang II-mediated growth. Thus, insulin can modulate the vascular RAS, and the effect of insulin on vascular growth may be via direct effects on angiotensinogen expression and translation operative through both the AT1 receptor and the conversion of Ang I to Ang II.

Angiotensin II↗
PubMed1997

Upregulation of angiotensin-converting enzyme during the healing process after injury at the site of percutaneous transluminal coronary angioplasty in humans.

BACKGROUND: Balloon injury models in rat have shown enhanced expression of ACE in the developing neointima. However, neointimal lesions in human coronary arteries are complex due to atherosclerosis and different types of wall laceration. This study was designed to investigate whether ACE is present in the neointima of humans, including patients with restenosis after percutaneous transluminal coronary angioplasty (PTCA). METHODS AND RESULTS: Thirty-seven sites with angioplasty injury, obtained at autopsy, were studied using immunocytochemical techniques. Sites with injury limited to a fibrous plaque and those with injury extending into the media (<2 months after PTCA) showed fibrocellular repair tissue composed mainly of smooth muscle cells that were distinctly positive for ACE. In cellular reactions at the site of injury limited to the atheromatous plaque (<2 months after PTCA), the expression of ACE appeared first in accumulated macrophages; once smooth muscle cells appeared in the repair tissue, they also expressed ACE. At a later stage (3 months after PTCA), the number of cells with ACE expression decreased markedly; from 7 months on, ACE was no longer expressed within the repair tissue. Basically, there were no differences with regard to ACE expression during the healing process after PTCA between segments with and those without angiographic evidence of restenosis. CONCLUSIONS: These results show that PTCA injury in humans results in upregulation of ACE at sites of active repair and, therefore, ACE could play an important role as one of the mediators of the healing process after PTCA.

Aged↗
PubMed1997

Trp64Arg mutation of beta3-adrenergic receptor in essential hypertension: insulin resistance and the adrenergic system.

A putative pathogenic mutation in the beta3-adrenergic receptor gene (Trp64Arg) has been reported to be associated with higher diastolic blood pressure as well as clinical features of the insulin resistance syndrome and an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM) in Pima Indians and Finns. Because essential hypertension is reported to be associated with insulin resistance, we studied the mutation in Japanese patients with essential hypertension to clarify associations of this mutation with hypertension, insulin resistance, and basal adrenergic state in hypertensive subjects. The allele frequency of the mutation (Arg) in patients with essential hypertension was similar to that in control subjects (35 of 202 alleles [17.3%] v 27 of 146 [18.5%], respectively, P > .7). Insulin sensitivity measured by hyperinsulinemic euglycemic glucose clamp and plasma norepinephrine and epinephrine levels were also similar in hypertensive subjects with and without the mutation. These data suggest that Trp64Arg mutation in the beta3-adrenergic receptor gene does not play a major role in susceptibility to essential hypertension or in insulin resistance and basal adrenergic state in hypertension.

Adult↗
PubMed1997

Insulin resistance is related to silent cerebral infarction in patients with essential hypertension.

Recently, hyperinsulinemia or insulin resistance has been suggested to be a risk factor for cardiovascular diseases. We evaluated the role of insulin resistance in the occurrence of silent cerebral infarction in 28 patients with essential hypertension (40 to 75 years, 157 +/- 4/89 +/- 2 mm Hg). Patients with diabetes mellitus or obesity (BMI > or = 30) were excluded. Insulin resistance was evaluated by means of constant glucose infusion rate (M value) during euglycemic-hyperinsulinemic glucose clamp test. Infarction was defined as a focal area with prolonged T1 and T2 relaxation times that was > 5 mm in diameter on brain magnetic resonance imaging. The severity of periventricular hyperlucency was evaluated by the distribution of the high intensity area. The number of silent infarctions significantly correlated only with the M value (F = 7.58, R2 = 0.23, P = .01) in multiple regression analysis using all variables: age, blood pressure, smoking history, lipid profile, levels of plasma glucose and insulin on fasting, and total amounts during 75-g OGTT. However, the severity of periventricular hyperlucency did not show a correlation with any factors. The occurrence of cerebral infarction was significantly correlated with thickening of the intima-media complex (IMC) of the common carotid artery on B-mode ultrasonography (F = 8.43, R2 = 0.25, P < .01). In conclusion, insulin resistance and thickening of IMC show a close relationship with the occurrence of silent cerebral infarction. Therefore, it may be important to improve insulin resistance for prevention of cerebral infarction in essential hypertensives.

Carotid Arteries↗
PubMed1997

Polymorphism of angiotensin converting enzyme, angiotensinogen, and apolipoprotein E genes in a Japanese population with cerebrovascular disease.

The homozygous deletion allele of the angiotensin converting enzyme gene (ACE/DD), homozygous threonine allele of the angiotensinogen gene (AGN/TT), and the epsilon4 allele of the apolipoprotein E gene (apoE/epsilon4) are reported to be associated with ischemic heart disease. Cerebrovascular disease (CVD) is another atherosclerotic disease; and the effects of these polymorphisms on CVD have been confusing. In this study, we investigated whether ACE/DD, AGN/TT, and apoE/epsilon4 genotypes are associated with CVD and whether genetic risk is enhanced by the effect of one upon another. We ascertained these genotypes in patients with cerebral infarction (n = 55) and cerebral hemorrhage (n = 38), diagnosed by brain computed tomography. Control subjects for the infarction group and the hemorrhage group were randomly selected from 583 subjects matched for age, gender, and history of hypertension with patients. Frequency of ACE/DD genotype was higher in the patients with infarction than in the controls (chi2 = 6.1, P < .05). The AGN/TT genotype was not associated with either infarction or hemorrhage, but it increased the relative risk for cerebral infarction in the subjects with ACE/DD genotype (chi2 = 8.0, P < .01, odds ratio; 11.7, 95% confidence intervals: 1.4 to 96.0). There was no significant association between apoE/epsilon4 and CVD. These results suggest that ACE/DD predicts cerebral infarction, but not cerebral hemorrhage, and that AGN/TT enhances the risk for cerebral infarction associated with ACE/DD.

Adult↗
PubMed1997

Renal effects of an angiotensin II antagonist in stroke-prone spontaneously hypertensive rat.

We evaluated the renal effects of the new angiotensin II type 1 (AT ) receptor antagonist, HR 720, in the stroke-prone spontaneously hypertensive rat. Rats were treated with either vehicle, HR 720, MK-954 (a selective AT1 receptor antagonist) or enalapril for 6 weeks. Blood pressure was decreased to a similar extent by HR 720, MK-954 and enalapril (203 +/- 4, 202 +/- 5 and 190 +/- 4 vs. 247 +/- 4 mm Hg for control). Urinary protein secretion was also decreased (5.2 +/- 0.3, 5.3 +/- 0.2 and 5.5 +/- 0.6 vs. 25.2 +/- 4.6 mg/100g/24h). The glomerular hypertensive change was improved in each drug-treated group (2.0 +/- 0.2, 3.3 +/- 0.3 and 1.6 +/- 0.1 vs. 17.6 +/- 1.5%; p < 0.0001). These results show that, in addition to its antihypertensive effect, HR 720 has a beneficial effect on renal function.

Angiotensin I↗
PubMed1997

Asp905Tyr polymorphism of protein phosphatase 1 G subunit gene in hypertension.

A possible pathogenic polymorphism in the gene for the G subunit of the glycogen-associated regulatory form of protein phosphatase 1 (PP1 G subunit), causing an Asp-to-Tyr substitution at codon 905 (Asp905Tyr), has been reported to be associated with insulin resistance and hypersecretion of insulin in the white population. Since marked heterogeneity has been reported in the association of mutations of candidate genes with essential hypertension between Japanese and other ethnic groups, we investigated the association of Asp905Tyr with essential hypertension in Japanese subjects. The frequency of the Tyr allele in Japanese control subjects (0.70) was much higher than that in the Danish population (0.10, P<1x10(-8)), indicating that the Tyr allele, previously reported as a rare variant in white subjects, is a common allele in our population. The genotype distribution in Japanese hypertensive patients (n=109; Asp/Asp=0.09, Asp/Tyr=0.39, Tyr/Tyr=0.52) was not significantly different (chi2=0.7, df=2, P>.6) from that in normotensive control subjects (n=148; Asp/Asp=0.12, Asp/Tyr=0.36, Tyr/Tyr=0.52). Among subjects with different PP1 G subunit genotypes, there was no difference in blood pressure, serum cholesterol, plasma glucose and insulin levels, and glucose disposal rate estimated by the euglycemic hyperinsulinemic clamp test. These data indicate that the Asp905Tyr polymorphism of the PP1 G subunit is not associated with essential hypertension, nor with insulin resistance and/or hyperinsulinemia in Japanese patients with essential hypertension, suggesting that the polymorphism plays little if any role in susceptibility to insulin resistance or hypertension.

Aged↗
PubMed1997

A case of arrhythmogenic right ventricular dysplasia with left and right ventricular hypofunction in an elderly subject--long-term follow-up.

A 72-year-old man was admitted with palpitations caused by sustained ventricular tachycardia. He had been followed for 27 years, with admissions on 7 occasions, on account of ventricular tachycardias, atrial fibrillation, and congestive heart failure. Electrophysiologic examination detected 2 points of origin of ventricular tachycardia in the right and left ventricles. During the examination a myocardial infarction led to death. At autopsy, most areas of the right ventricle and the left ventricular apex were found to have been replaced by fatty tissue, pointing to severe fatty infiltration into the myocardium. Thus, this patient represented a unique cause of arrhythmogenic right ventricular dysplasia (ARVD) with severe fatty degeneration causing progression of ARVD. It is important that a diagnosis of ARVD is made carefully and rigorously in elderly subjects.

Aged↗
PubMed1997

Influence of aging on progression of cardiovascular complications associated with insulin resistance in patients with essential hypertension.

Hyperinsulinemia or insulin resistance is suggested to play a role in the pathogenesis of hypertension and its target organ diseases. It is also well documented that aging is associated with a decline in glucose tolerance and insulin sensitivity, but there are few reports on the relationship between aging and insulin sensitivity or on the effects of aging on the progression of cardiovascular complications in patients with essential hypertension. To clarify these effects of aging in essential hypertension, 44 patients were examined by the euglycemic hyperinsulinemic glucose clamp test and ultrasonography of the heart and carotid arteries. There was a significant negative correlation between aging and insulin sensitivity (r = -0.37, p < 0.05). Significant increases in left ventricular mass index and carotid wall thickening accompanied by insulin resistance were seen in only non-elderly patients but not in elderly patients. These results suggest that aging decreases insulin sensitivity even in essential hypertensive subjects and that insulin resistance does not affect the progression of cardiac hypertrophy and atherosclerosis in elderly patients with essential hypertension.

Aged↗
PubMed1997

Recognition of tissue- and subtype-specific modulation of angiotensin II receptors using antibodies against AT1 and AT2 receptors.

Polyclonal antibodies have been prepared against synthetic peptides of human angiotensin II type-1 (AT1) and type-2 (AT2) receptors. Synthetic peptides corresponded to amino acids 15-24 of AT1 receptor and amino acids 241-253 of AT2 receptor. Western blot analysis of membranes from cell homogenates of COS-7 cells transfected with expression plasmids for mouse AT1b receptor, human vascular smooth muscle cells, and rat peripheral tissue demonstrated a major band of MW 44,000 with AT1 receptor antibody. Cell homogenates of COS-7 cells transfected with expression plasmids for human AT2 receptor showed a band of MW 44,000 with AT2 receptor antibody. Tissue homogenate of rat adrenal medulla and human pheochromocytoma presented a major band of MW 52,000 and a minor band of MW 44,000 with AT2 receptor antibody. AT1 receptor expression was in the following order: rat aorta > > lung, kidney, spleen, adrenal cortex > adrenal medulla, heart. Expression of AT2 receptor was in the following order: rat adrenal medulla > cortex, kidney, heart. Three-day treatment with CS866, an AT1 receptor antagonist, and temocapril, an angiotensin-converting enzyme inhibitor, suppressed AT1 receptor expression in the rat adrenal cortex, but not in the heart or adrenal medulla. AT2 expression was not affected by treatment with these drugs. These results suggest that newly developed antibodies for AT1 and AT2 receptors are useful in elucidating the regulation of subtype-specific receptor expression, and that AT1 but not AT2 receptors in adrenal tissue are regulated by angiotensin II.

Adrenal Glands↗
PubMed1996

Predominance of nocturnal sympathetic nervous activity in salt-sensitive normotensive subjects.

To assess the relation between salt sensitivity and autonomic nervous function by power spectral analysis of heart rate variability in normotensive subjects, low and high salt diets were given to 13 normotensive men (aged 25 to 39 years) for 4 days each. Autonomic function was assessed by power spectral analysis of R-R intervals based on an autoregressive algorithm from 24-h Holter electrocardiogram. Subjects whose mean blood pressure was increased more than 3 mm Hg by high salt diet were defined as salt sensitive (SS, n = 5), and the remainder as salt resistant (SR, n = 8). Using the low frequency (LF, 0.1 Hz) and high frequency (HF, 0.25 Hz) components, the LF to total power ratio (%LF) was used as a marker of sympathetic activity, and the HF to total power ratio (%HF) as a marker of parasympathetic activity. Compared to the daytime, SR revealed a decrease in %LF and an increase in %HF during the night on both diets. In SS, these circadian changes were observed only during low-salt diet. During the night, SS showed a higher %LF and a lower %HF than SR. Plasma catecholamines tended to be decreased by the high sodium diet in SR but not in SS subjects. These results suggest that the persistent nocturnal predominance of sympathetic nervous activity in a salt-sensitive men may contribute to the subsequent increase of blood pressure in these subjects.

Adult↗
PubMed1996

Impaired endothelial function with essential hypertension assessed by ultrasonography.

The objective of this investigation was to evaluate the role of hypertension in endothelial function, changes in which are known to be an early event of atherosclerosis. We assessed endothelial function in 13 subjects with normal blood pressure and 13 subjects with essential hypertension who had never been treated for hypertension or hyperlipidemia and who had no history of smoking or coronary or cerebrovascular disease. B-mode ultrasonography was used to measure the diameter of the brachial artery. Endothelium-dependent dilatation was assessed as the change in diameter of the artery during reactive hyperemia. Endothelium-independent dilatation was evoked, as a control, by sublingual administration of isosorbide dinitrate. Despite similar ages and lipid and glucose levels in the study groups, endothelium-dependent dilatation was less in patients with hypertension (13.1% +/- 1.6%) than in subjects with normal blood pressure (18.5% +/- 1.9%) (p < 0.05), whereas isosorbide dinitrate-induced changes were similar. Systolic and diastolic blood pressure were significantly correlated with endothelium-dependent vasodilatation (r = -0.57 and r = -0.53, respectively) but not with the change by isosorbide dinitrate. These results suggest that endothelial dysfunction exists in patients with hypertension and precedes overt atherosclerotic disease.

Adult↗
PubMed1996

Insulin resistance and cardiovascular complications in patients with essential hypertension.

Hyperinsulinemia or insulin resistance is suggested to play a role in the pathogenesis of hypertension and its target organ diseases. We designed this study to evaluate the role of insulin resistance in cardiac function, cardiac hypertrophy, wall thickness of the common carotid artery, and endothelial function of the brachial artery in essential hypertensive patients without diabetes mellitus. Insulin resistance was evaluated by the constant glucose infusion rate (M value) during the euglycemic-hyperinsulinemic glucose clamp test. In correlation analysis for several indices of glucose metabolism, only M value correlated with left ventricular mass index (LVMI), ratio of peak velocity during atrial contraction to that during early left ventricular filling phase (E/A ratio) and intima-media complex (IMC). In stepwise regression analysis of various risk factors for cardiovascular diseases, only M value and age were dependent factors for LVMI, E/A ratio, and IMC. No indices of glucose metabolism or risk factors for cardiovascular diseases correlated with endothelium-dependent and -independent vasodilation. These results suggest that insulin resistance, but not glucose intolerance and hyperinsulinemia, partly accelerates cardiovascular complications such as left ventricular hypertrophy and wall thickening of the carotid artery in patients with essential hypertension.

Blood Flow Velocity↗