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Biomedical subjects

H Rakugi

Publications and source records attributed to H Rakugi.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1997

[Glucose tolerance and insulin resistance in the elderly].

Glucose tolerance is reported to be impaired in the elderly, and this is said to be mainly due to a decrease in insulin sensitivity (insulin resistance). Insulin resistance is known to be associated with atherosclerosis and coronary artery disease. To clarify whether or not age-dependent changes in glucose tolerance and insulin sensitivity are risk factors for coronary artery disease, as they are in the case of the insulin resistance syndrome, we studied age-dependent changes in glucose tolerance, insulin sensitivity, blood pressure, and serum lipids in a large number of subjects who underwent annual health check-ups, and then studied the relationships between coronary artery disease and aging, insulin sensitivity, and other risk factors in subjects who underwent coronary angiography. Aging was associated with an increased prevalence of noninsulin-dependent diabetes mellitus and impaired glucose tolerance; even in subjects with normal glucose tolerance, plasma glucose levels during an oral glucose tolerance test were significantly higher in the elderly. Insulin sensitivity, as assessed by the ratio of the sum of the plasma glucose divided by the sum of the serum insulin during the test (sigma PG/sigma IRI), was significantly lower in subjects over 60 years old than in younger subjects. Age-dependent impairment of insulin sensitivity and glucose tolerance was associated with increased blood pressure and serum cholesterol levels, but not with changes in boy mass index or serum triglyceride levels. As an independent variable, aging, but not insulin sensitivity, was related to the severity of coronary artery disease. These data suggest that aging is associated with glucose intolerance, insulin resistance, and an increased risk of coronary artery disease, but that the effect of aging on coronary artery disease cannot be explained by insulin resistance alone. Other factors, such as glucose intolerance and increased blood pressure, in addition to insulin resistance, appear to be responsible of the increased risk for coronary artery disease in the elderly.

Aged↗
PubMed1997

[Angiotensin receptor antagonist for therapy of patients with hypertension].

Nonpeptide angiotensin II type 1-receptor antagonists, AT1 receptor antagonists are newly developed and useful drugs for hypertension and congestive heart failure. In Japan, the efficacy and safety of losartan and candesartan cilexetil in patients with essential hypertension have been evaluated by the double-blind, parallel group-comparison study using enalapril as control drug. Both trials revealed that these drugs showed a hypotensive effect comparable to that of enalapril with a high safety since the adverse drug reaction of cough was recognized in very few patients. Furthermore, a recent randomised trial of losartan versus captopril in patients over 65 with heart failure, evaluation of losartan in the elderly study (ELITE), showed that losartan was associated with a lower mortality than that found with captopril. Further studies will clarify differences in protection of cardiovascular system with a long-term treatment between AT1, receptor antagonists and angiotensin-converting enzyme inhibitors.

Aged↗
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↗
PubMed1996

Polymorphism of the apolipoprotein E and angiotensin-converting enzyme genes in Japanese subjects with silent myocardial ischemia.

The apolipoprotein epsilon4 allele and homozygous deletion allele (DD) of the angiotensin-converting enzyme gene are reported to be associated with an increase in the incidence of ischemic heart disease. In this study, we examined whether the apolipoprotein epsilon4 genotype and angiotensin-converting enzyme/DD allele are associated with silent myocardial ischemia. We screened 3920 subjects undergoing general checkups who no symptoms of ischemic heart disease. Seventy subjects (2 percent) showed ischemic ST-segment depression during the double two-step exercise test. One hundred and twenty control subjects without ischemic ST-segment depression were recruited from the same population and matched for sex, age, and blood pressure. We performed genotyping of the apolipoprotein E gene (epsilon2, epsilon3, and epsilon4) and angiotensin-converting enzyme gene (I and D) using polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction, respectively. Allele frequently of epsilon4 of the apolipoprotein E gene was higher in the ischemic group (11 percent) than the nonischemic group (5 percent) (chi2 = 5.35, P < .05), but there was no significant association between the allele or the genotype frequency of the angiotensin-converting enzyme gene and the incidence of ischemic ST-segment depression. Furthermore, stepwise multiple regression analysis also revealed that total cholesterol level and epsilon4 genotype were predictors of ischemic change in the exercise tolerance test (chi2 = 12.8, P < .005, R(2) = .051). These results suggest that the apolipoprotein epsilon4 allele is an independent genetic risk factor for silent myocardial ischemia in Japanese subjects.

Adult↗
PubMed1996

Analysis and comparison of new candidate loci for hypertension between genetic hypertensive rat strains.

To search for the genes that determine the level of blood pressure, we performed linkage analyses using rat microsatellite markers in two sets of F2 rats derived from two hypertensive rat strains and one normotensive rat strain. In the first F2 progeny obtained from spontaneously hypertensive rats and Wistar-Kyoto rats, it was found that two different loci cosegregated with blood pressure. One was gamma-crystallin locus on rat chromosome 9, which has a hypertensive effect, and the other was peroxisomal 3-keto acyl-CoA thiolase locus on rat chromosome 8, which has a hypotensive effect. Then, we studied the same loci in second F2 progeny obtained from Dahl/Iwai salt-sensitive rats and Wistar-Kyoto rats. It was found that the locus located on rat chromosome 8 also had a hypotensive effect, although the others were not cosegregated with blood pressure in this cross. We suggest that a new locus for hypertension is located on rat chromosome 9 and that a locus on rat chromosome 8 has a common effect that makes blood pressure decrease in different hypertensive strains.

Animals↗
PubMed1996

Analysis of candidate genes for insulin resistance in essential hypertension.

To clarify the genetic basis of insulin resistance in hypertension, case-control association studies were performed to examine candidate genes for insulin resistance in hypertension. Since the main site of insulin resistance in hypertension is glycogen synthesis in skeletal muscle, genes that encode molecules involved in this pathway, i.e. insulin receptor (INSR), insulin-responsive glucose transporter (GLUT4) and glycogen synthase (GSY), were studied. In addition, since recent studies suggest the contribution of beta3 adrenergic receptor to the insulin resistance syndrome, the gene encoding beta3 adrenergic receptor (ADRB3) was also studied. Frequency of homozygotes for common C allele of a microsatellite polymorphism in the INSR gene was higher in the hyperinsulinemia group, but not in the normoinsulinemia group of hypertensive patients than in normotensive control subjects. Insulin sensitivity, however, was not significantly different between hypertensive patients with C/C genotype and those without this genotype. No significant differences were observed in the distribution of alleles or genotypes of the GLUT4, GSY and ADRB3 genes between hyperinsulinemia and normoinsulinemia groups of hypertensive patients or between these groups and the control group. These data suggest that the INSR polymorphism is associated with hyperinsulinemia, but not with insulin resistance, in hypertension.

Case-Control Studies↗
PubMed1996

[Primary biliary cirrhosis with polymyositis successfully treated with prednisolone and ursodeoxycholic acid].

A 65-year-old woman was given a diagnosis of polymyositis in April 1991. She was treated with prednisolone until December 1993, at which time muscle strength had increased and high blood pressure had developed. In May 1994 she was hospitalized for muscle weakness and mild liver dysfunction. Prednisolone was given and the levels of hepatobiliary enzymes decreased. Immunological examination revealed strongly positive results for anti-mitochondria antibody and M-2 antibody, which lead to the diagnosis of primary biliary cirrhosis. administration of ursodeoxycholic acid in addition to prednisolone was followed by normalization of liver function and a decrease in the production of the autoantibodies. Although polymyositis can be complicated by autoimmune diseases, reports of complication by primary biliary cirrhosis are rare, here we report that treatment with the combination of ursodeoxycholic acid and prednisolone was successful in a patient with liver dysfunction and primary biliary cirrhosis.

Aged↗
PubMed1996

Links between hypertension and myocardial infarction.

The mechanisms through which hypertension contributes to the occurrence of myocardial infarction should be discussed from two points of view: (1) common risk factors for the two diseases, such as genetic risk, insulin resistance, sympathetic hyperactivity, and vasoactive substances such as angiotensin K, and (2) linking factors that are induced by hypertension and contribute to the development of atherosclerosis and myocardial infarction, such as atherosclerosis and left ventricular hypertrophy. Mechanical stress on blood vessels because of high blood pressure is an especially important factor in endothelial dysfunction, the progression of atherosclerosis, and plaque rupture. This article concentrates on these factors from the perspective of their relationship with the renin-angiotensin system, because recent multicenter trials have demonstrated that angiotensin-converting enzyme inhibitors are effective for preventing recurrence of myocardial infarction.

Arteriosclerosis↗
PubMed1995

Enhancement of insulin sensitivity by troglitazone lowers blood pressure in diabetic hypertensives.

The association of hypertension with insulin resistance has been reported. Troglitazone (CS-045) is a newly developed antidiabetic agent that enhances insulin sensitivity. Its antidiabetic effects have been confirmed in diabetic animals and patients. The present study was performed to evaluate whether the amelioration of hyperinsulinemia by troglitazone lowers blood pressure in essential hypertensives. Troglitazone was administered orally to 18 outpatients with essential hypertension complicated by mild diabetes at a dose of 200 mg twice a day for 8 weeks. Blood pressure was decreased from 164 +/- 3/94 +/- 2 mm Hg to 146 +/- 3 (P < .001)/82 +/- 3 (P < .05) mm Hg at 8 weeks of the treatment period. Pulse rate did not change. Fasting plasma glucose changed from 159 +/- 10 mg/dL to 144 +/- 14 mg/dL at 8 weeks (P < .05). Plasma insulin (IRI) levels changes from 9.1 +/- 1.2 microU/mL to 6.3 +/- 0.8 microU/mL at the endpoint of treatment (P < .1). Decrease in mean blood pressure from the control period to the endpoint of the treatment correlated significantly with decrease in IRI (r = 0.59, P < .05). In summary, troglitazone treatment induces improvement in both glucose metabolism and blood pressure control in essential hypertensive patients with diabetes mellitus. These results suggest that insulin resistance or plasma insulin level plays a role in the pathogenesis of essential hypertension.

Aged↗
PubMed1995

Effect of an antihypertensive drug on brain angiotensin II levels in renal and spontaneously hypertensive rats.

1. Although numerous studies suggest that brain angiotensin (AII) may play an important role in the regulation of blood pressure, it is still unclear what factors may influence brain AII. In this study, we hypothesized that brain AII is influenced by circulating factors. To investigate the role of blood pressure and plasma AII in brain AII level, we studied the effect of an antihypertensive drug on brain AII in two-kidney, one-clip (2K1C) and spontaneously hypertensive (SHR) rats. 2. Hydralazine (20 mg/kg per day) and vehicle (water) were given to 2K1C rats between 2 and 6 weeks after operation and SHR for 4 weeks. In addition, vehicle was applied to sham operated rats and Wistar-Kyoto (WKY) rats. Brain and plasma AII was measured by a highly sensitive radioimmunoassay coupled with high performance liquid chromatography. 3. Hydralazine treatment effectively lowered blood pressure to the same level of sham-operated and WKY rats. 2K1C rats showed significantly higher plasma AII than sham rats, but hydralazine treatment did not show any change in plasma AII. Brain AII in the hypothalamus region of 2K1C rats showed a significantly higher level than sham rats. Interestingly, hydralazine treatment diminished this increase in brain AII. In contrast, SHR showed higher brain AII levels in the hypothalamus, brainstem and cerebellum than in WKY rats, whereas there was no significant change in plasma AII concentration between SHR and WKY rats. In contrast to the results found in 2K1C rat experiments, hydralazine treatment failed to decrease brain AII levels despite lowered blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

Enhanced predictability of myocardial infarction in Japanese by combined genotype analysis.

To explore the genes responsible for myocardial infarction and restenosis after percutaneous transluminal coronary angioplasty, we performed association studies of the polymorphisms of the angiotensinogen and angiotensin-converting enzyme (ACE) genes. In the first study, normotensive myocardial infarction patients (n = 103) and control subjects (n = 103), who were matched for established risk factors with the myocardial infarction patients, were randomly selected. The angiotensinogen-TT genotype (T indicates threonine instead of methionine at position 235) was more frequent in the myocardial infarction group than in the control group (P < .05). The ACE-DD genotype (D indicates a deletion polymorphism in intron 16) was also more frequent in the myocardial infarction group (P < .0001). The odds ratio estimated by the combined analysis of the angiotensinogen-TT and ACE-DD genotypes (11.2) was markedly increased compared with that estimated separately from the angiotensinogen-TT (1.75) or ACE-DD (4.43) genotype. In the second study, we investigated 91 consecutive patients with acute myocardial infarction who underwent successful direct angioplasty. Combined analysis showed that the angiotensinogen-TT genotype did not enhance the predictability of myocardial infarction from the ACE-DD genotype. In conclusion, the angiotensinogen-TT genotype is a predictor for myocardial infarction, as well as the ACE-DD genotype, and the combined analysis of the angiotensinogen-TT and ACE-DD genotypes further enhanced the predictability of myocardial infarction in Japanese, suggesting its future clinical usefulness.

Angioplasty, Balloon, Coronary↗
PubMed1995

Angiotensin I-converting enzyme gene polymorphism is associated with myocardial infarction, but not with retinopathy or nephropathy, in NIDDM.

OBJECTIVE: To clarify the relationship between the angiotensin I-converting enzyme (ACE) gene polymorphism and diabetic micro- and macroangiopathy in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: We examined 267 NIDDM patients with various stages of diabetic retinopathy, 61 patients with myocardial infarction (MI), and 136 patients without MI. An insertion/deletion polymorphism of the ACE gene was typed by polymerase chain reaction. RESULTS: Although no association was found between ACE gene polymorphism and diabetic retinopathy or nephropathy, this polymorphism was associated with MI in the patients with NIDDM. Homozygotes for the deletion polymorphism (DD genotype) were found more frequently in diabetic patients with MI (31.1%) than in diabetic patients without ischemic heart disease (16.9%), with a relative risk of 2.22 (95% confidence interval 1.11-4.46, P = 0.024). CONCLUSION: These data indicate that ACE gene polymorphism is associated with MI, but not with retinopathy or nephropathy, in patients with NIDDM and suggest that the ACE gene confers susceptibility to diabetic macroangiopathy but not to microangiopathy.

Alleles↗
PubMed1994

Augmentation by converting enzyme inhibition of accelerated endothelin release from rat mesenteric arteries following nephrectomy.

We investigated the release of endothelin-1 (ET) from rat mesenteric arteries to clarify its pathophysiological role in the sustained hypertension of spontaneously hypertensive rats (SHR) following nephrectomy and the regulatory mechanism of the ET release which might be modified by vascular angiotensins and bradykinins. Nephrectomy increased the plasma level of ET and enhanced the ET release in both SHR and Wistar-Kyoto rats (WKY). CV-11974, an angiotensin II receptor antagonist, did not affect the ET release from arteries of nephrectomized rats. On the contrary, infusion of captopril, a converting enzyme inhibitor, further enhanced the ET release in both intact and nephrectomized rats. These findings suggest that the release of ET from mesenteric arteries may be regulated by bradykinins, but not by angiotensins. This pressor substance does not contribute to the sustained hypertension because the enhanced production of ET observed in both SHR and WKY. However, there is a possibility that the exaggerated responsiveness of vascular ET may in part account for local vascular tone and vascular remodeling in renal dysfunction.

Analysis of Variance↗
PubMed1994

Antihypertensive effects of the neutral endopeptidase inhibitor SCH 42495 in essential hypertension.

The antihypertensive effects and safety of a novel neutral endopeptidase inhibitor, SCH 42495, were investigated in hypertensive patients. A multicenter, open clinical trial was conducted in 27 patients with essential hypertension, WHO Stage I or II. Mean age was 64 +/- 1 years. After 2 to 4 weeks of a placebo run-in, 50 mg twice daily, was started, with the dose increased to 100 mg twice daily, and 200 mg twice daily, every 2 weeks, if necessary, to achieve a predetermined response. Blood pressure and pulse rate were monitored every 2 weeks. Blood chemistry, plasma atrial natriuretic peptide (ANP), and plasma cGMP levels were determined before and after the 8-week treatment period. Blood pressure was significantly reduced, from 171 +/- 1/100 +/- 1 mm Hg to 146 +/- 3/84 +/- 2 mmHg (P < .001) at the end of the 8-week treatment period. No change in pulse rate was noted. Efficacy rate was evaluated in 25 patients treated for 4 weeks or more. Efficacy rate was 44% with 50 mg twice daily, 60% with 100 mg twice daily, and 80% with 200 mg twice daily. Adverse reactions such as headaches and palpitation were observed in six patients (22.2%), with treatment discontinued in five. Significant correlation was observed between increment in plasma ANP levels and blood pressure reductions (r = -0.53, P < .05). Increase in plasma cGMP was positively correlated with increments in plasma hANP (r = 0.80, P < .001). SCH 42495 has potent antihypertensive effect associated with an enhancement of endogenous hANP and may be clinically useful as a new class of antihypertensive drug.

Aged↗