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N Ura

Publications and source records attributed to N Ura.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effect of an angiotensin II receptor antagonist, candesartan, on insulin resistance and pressor mechanisms in essential hypertension.

Candesartan (8 mg/d) was administered for 2 weeks to eight patients with essential hypertension to investigate the effect of an angiotensin II receptor antagonist on insulin sensitivity. The effect of candesartan on sodium-retaining action and the activation of pressor systems by hyperinsulinaemia, which might be related to pressor mechanisms in essential hypertension, was also investigated in this study. In patients with essential hypertension, candesartan restored insulin sensitivity to the level of that in normotensive subjects. Candesartan treatment attenuated the sodium-retaining action of hyperinsulinaemia. These findings suggest that inhibition of angiotensin II action by candesartan can improve insulin sensitivity and inhibit the sodium-retaining action associated with hyperinsulinaemia in essential hypertension.

Angiotensin Receptor Antagonists↗
PubMed1999

Changes of urinary dopamine excretion early after balloon mitral commissurotomy in mitral stenosis.

1. In order to investigate the changes of reduced urinary free dopamine excretion (uDA) in heart failure, 15 patients with symptomatic mitral stenosis were investigated on their uDA, endogenous creatinine (Cr) clearance, urinary excretion of sodium (UNaV), fractional excretion of sodium (FENa), plasma noradrenaline (pNA) and plasma L-dopa concentration before and early after percutaneous transvenous mitral commissurotomy (PTMC) by the clearance study. The delivery of L-dopa to renal proximal tubules (plasma L-dopa x Cr clearance), and the conversion ratio of plasma L-dopa to urinary dopamine in the kidney [uDA/(plasma L-dopa x Cr clearance)] were also estimated. 2. After successful PTMC, uDA, UNaV and FENa showed a significant but incomplete improvement and the changes of uDA were correlated positively with those of cardiac index (CI) (r = 0.665, P < 0.01), not with changes of pulmonary wedge pressure. While plasma L-dopa and plasma L-dopa x Cr clearance improved, uDA/(plasma L-dopa x Cr clearance) was not significantly changed early after PTMC. 3. From these results, it was suggested that reduced uDA tended to increase incompletely in relation with functional recovery of heart, and that increased plasma L-dopa and a delivery of L-dopa to renal proximal tubules have some positive role on urinary dopamine excretion, at least, early after PTMC.

Adult↗
PubMed1999

Mobile intracardiac calcinosis: a new risk of thromboembolism in patients with haemodialysed end stage renal disease.

Cardiac calcinosis is a common complication of end stage renal disease. A newly observed risk of thromboembolism is reported in four patients with mobile cardiac calcinosis, treated with long term dialysis. Rapidly growing mobile calcification was confirmed by echocardiography. Each patient had an imbalance in serum calcium x inorganic phosphate (Ca x P product >/= 50); this imbalance could not be treated due to the sudden death of the patient or the need for surgical resection to prevent recurrent cerebral thromboembolism. Histological examination revealed intracardiac calcinosis in three cases, and each case showed haemodialysis hypoparathyroidism (intact PTH < 160 pg/ml). Thromboembolism in such cases is rare, however it indicates a need for cautious echocardiographic monitoring in end stage renal disease in patients with an uncontrolled Ca x P product.

Aged↗
PubMed1999

The contribution of nitric oxide to diuretic and natriuretic effects of renal kinins in normotensive rats.

We have reported that diuresis and natriuresis due to increase in renal kinins induced by the neutral endopeptidase 24.11 (NEP) inhibitor were attenuated by nitric oxide (NO) synthase inhibitor. To further clarify the water-sodium excretory mechanism of renal kinins, we estimated NO2+NO3 (NOx) and cGMP in plasma and urine with and without a specific NEP inhibitor, thiorphan. P-aminohippuric acid (PAH) and inulin were injected into male Sprague-Dawley rats. Vehicle (n = 8) or thiorphan (30 mg/kg, n = 10) was injected after the control period. Mean blood pressure (MBP), plasma and urinary PAH, inulin, NOx and cGMP, urinary volume (UV) and urinary sodium excretion (UNaV) were measured before and after injection of the reagents. MBP, renal plasma flow and glomerular filtration rate were not affected by thiorphan. Plasma NOx and cGMP with thiorphan did not differ from the vehicle, while urinary NOx and cGMP increased. None of the variables were affected by vehicle. UV and UNaV were higher with thiorphan than with vehicle. Positive correlation was found between urinary deltaNOx and deltacGMP. Each urinary deltaNOx and deltacGMP was significantly correlated to both deltaUV and deltaUNaV. Urinary NOx and cGMP were increased while maintaining correlations to UV and UNaV, but plasma NOx and cGMP were not affected by thiorphan. This implies that the mechanism of water-sodium excretion induced by NEP inhibitor is mediated by renal NO. Therefore, renal NO may contribute to the diuretic and natriuretic effects of renal kinins.

Animals↗
PubMed1999

Role of hyperinsulinemia in atherosclerotic coronary arterial disease: studies of semi-quantitative coronary angiography.

OBJECTIVE: To evaluate the role of insulin resistance on coronary atherosclerosis, angiographic semiquantitative scores of coronary stenosis and calcification were evaluated. SUBJECTS AND METHODS: Ninety-five non-diabetic subjects with coronary arterial disease were selected from our angiographic data base. Hyperinsulinemia was defined as a serum insulin level of > or = 60.4 IU/l at 120 minutes after 75 g oral glucose challenge. RESULTS: Twenty-three (24%) of the patients exhibited hyperinsulinemia. There was no difference in age or gender between the two subgroups. The incidence of hypertension, smoking habits, hypercholesterolemia, and hyperuricemia were also the same among the insulin resistance subgroups. Subjects with hyperinsulinemia had higher coronary artery scores of stenosis (11.9+/-5.6 vs 8.3+/-5.0, p<0.0001) and calcification (7.5+/-6.3 vs 4.8+/-4.9, p<0.0001). Moreover, the stenosis score had a close linear correlation with the 120 minutes serum insulin level (r=0.266, p=0.009), but not with the fasting level. CONCLUSION: These results suggest that hyperinsulinemia is a risk for coronary arterial disease, and emphasize the severity of coronary atherosclerosis in normal glucose tolerant subjects.

Adult↗
PubMed1998

Effects of the angiotensin converting enzyme inhibitor temocapril on insulin sensitivity and its effects on renal sodium handling and the pressor system in essential hypertensive patients.

The effects of the angiotensin converting enzyme (ACE) inhibitor temocapril on insulin sensitivity and its effects on renal sodium handling and the pressor system were investigated in essential hypertensive patients (EHT). Seven EHT were hospitalized and underwent a 2-h euglycemic hyperinsulinemic glucose clamp before and after 2 weeks' administration of temocapril (4 mg/day). Insulin sensitivity was calculated using the M value from the infusion rate of glucose with hyperinsulinemia using the glucose clamp method. Renal clearances of sodium, lithium, creatinine, and paraaminohippuric acid were used to calculate fractional proximal and distal tubular reabsorption of sodium (FPR(Na), FDR(Na)) and renal plasma flow (RPF) before and during insulin infusion by the glucose clamp method. Temocapril decreased blood pressure and increased M value significantly. Before temocapril treatment, hyperinsulinemia by the glucose clamp induced significant decreases of urinary excretion of sodium (U(Na) V) and fractional excretion of sodium (FENa). After treatment, these decreases were attenuated, and the change of U(Na) V (deltaU(Na) V) with hyperinsulinemia was significantly higher and deltaFENa showed a higher tendency, compared with before the treatment. FPR(Na) showed no change with hyperinsulinemia before treatment, but significantly decreased after treatment. DeltaFPR(Na) was significantly lower after treatment than that before treatment. FDR(Na) showed an increase with hyperinsulinemia, and deltaFDR(Na) was similar between before and after treatment. RPF showed no change with hyperinsulinemia, and no difference was found in deltaRPF between before and after treatment. Plasma norepinephrine level (PNE) and plasma renin activity (PRA) showed increases, whereas plasma aldosterone concentration (PAC) did not change with hyperinsulinemia. There were no significant differences in deltaPNE, deltaPRA, and deltaPAC between before and after treatment. From these results, it is suggested that in EHT 1) temocapril improves insulin resistance, and 2) although temocapril shows no significant influence on the augmentation of pressor systems by hyperinsulinemia, this agent attenuates the sodium-retaining action of hyperinsulinemia, which may be attributable to suppression of insulin-induced sodium reabsorption at the proximal tubules. These effects may lead to additional beneficial effects in the treatment of essential hypertensives with insulin resistance.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Effects of aging on the insulin actions for the glucose metabolism and renal function in normotensives and essential hypertensives.

It has been suggested that hyperinsulinemia compensating insulin resistance in glucose metabolism may be a pathogenic factor in essential hypertension. On the other hand, age-associated increases in the prevalence of glucose intolerance and hypertension are also well established. The aim of this study is to clarify the influence of aging on insulin sensitivity in glucose metabolism and on renal sodium handling under hyperinsulinemia, which may relate to high blood pressure in insulin-resistant subjects. Fifty-two normotensive subjects and 61 patients with essential hypertension were evaluated in this study. The subjects of these groups were divided into young (<40 years old) and middle-elderly (> or = 40 years old): young normotensives (Y-NT, n = 22); middle-elderly normotensives (ME- NT, n = 30); young hypertensives (Y-HT, n = 9); and middle-elderly hypertensives (ME-HT, n = 52). Using the euglycemic hyperinsulinemic glucose clamp, insulin sensitivity was assessed as M value. Just before the start and the termination of the glucose clamp, creatinine clearance (Ccr) and urinary excretion of sodium (UNaV) were measured. In addition, renal plasma flow assessed as para-aminohippuric acid clearance was also measured at the same time in several subjects; 8 Y-NT, 8 ME-NT, 3 Y-HT, and 10 ME-HT. The M value was significantly lower in ME-NT, Y-HT, and ME-HT, compared to Y-NT, although blood sugar and immunoreactive insulin levels were similar in all four groups. In normotensive subjects, there was a significant, negative correlation between age and M value. However, this correlation was not observed in hypertensive patients. UNaV decreased in ME-NT, Y-HT, and ME-HT, but not in Y-NT under hyperinsulinemia by the glucose clamp, whereas Ccr showed no significant change in any group. In all subjects, the change of UNaV (deltaUNaV) correlated significantly and positively with the M value. Renal plasma flow significantly increased under hyperinsulinemia by the glucose clamp in only Y-HT, but not in the other groups. There was a significant, positive correlation between deltaUNaV and the change of renal plasma flow under hyperinsulinemia by the glucose clamp. These results suggested that both the impairments of the insulin sensitivity and insulin-induced vasodilation at the renal artery with aging may partially contribute to age-related elevation of blood pressure through renal sodium retention by compensating hyperinsulinemia. On the other hand, it seems reasonable to assume that these abnormalities, which can contribute to high blood pressure in essential hypertension, already may exist at lower ages in essential hypertensive patients.

Adolescent↗
PubMed1998

Endogenous immunoreactive ouabain-like and digoxin-like factors in reduced renal mass hypertensive rats.

We evaluated the urinary excretion of immunoreactive endogenous ouabain-like factor (OLF) and digoxin-like factor (DLF) to investigate their pathophysiological roles in sodium metabolism and blood pressure in 5/6-reduced renal mass rats, a model of volume-expanded hypertension. About five-sixths of the kidney mass (5/6 RRM, n = 9) was removed from male Sprague-Dawley rats, or the rats were sham operated (control, n = 10). Both groups were fed regular diets with tap water for 1 wk as a control period, followed by 1% saline solution for 4 wk. Systolic blood pressure (SBP), urine volume (UV), urinary sodium excretion (UNaV), DLF, and OLF were measured on the last 2 d of every week throughout the experimental period. SBP and UNaV were significantly higher in 5/6 RRM rats than in control rats. Urinary DLF significantly increased, reaching peak value in the first week, while OLF increased continuously, reaching peak value in the fourth week. In the first week, there were a significant positive correlations between the change in DLF and the changes in UNaV and SBP. However, the change in OLF was not correlated with changes in either UNaV or SBP. Both SBP and UNaV showed a significant positive correlation with OLF (p<0.001, r=0.547, p<0.001, r=0.658, respectively), whereas DLF significantly correlated with UNaV (p< 0.001, r= 0.584) but not with SBP in 5/6 RRM. These findings suggest that endogenous OLF and DLF coexist in rat urine and that an increased level of OLF, but not DLF, may contribute to the development and maintenance of hypertension. DLF may contribute to renal sodium excretion in this volume-expanded hypertensive rat model.

Animals↗
PubMed1998

Association of insulin resistance and hyperinsulinemia with disturbed lipid metabolism in patients with essential hypertension.

To clarify the association of insulin resistance and hyperinsulinemia with lipid metabolism in patients with essential hypertension (EHT), we used the euglycemic hyperinsulinemic glucose clamp technique (GC) and the 75-g oral glucose tolerance test (OGTT) to compare the characteristics of glucose and lipid metabolism in insulin-resistant patients with essential hypertension (EHT-R) with those in insulin-non-resistant patients with essential hypertension (EHT-N) and normotensive subjects (NT). Twenty-eight NT and 42 EHT whose body mass index (BMI) was less than 28 kg/m2 were studied to eliminate the effects of obesity on insulin sensitivity and lipid metabolism. Insulin sensitivity was evaluated by GC and expressed as metabolic clearance rate of glucose (M value, mg/m2/min). Mean -ISD of the M value in NT (145.0 mg/m2/min) was chosen as the cutoff point for insulin resistance. On the basis of this value, 33.3% of the EHT were EHT-R. There was no significant difference in age or BMI among the three groups. Blood samples were collected before GC to measure levels of total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), and HDL cholesterol (HDL-C). EHT-R had significantly higher levels of fasting blood sugar, fasting immunoreactive insulin, insulin at 120 min (IRI-120), and summation of insulin or blood sugar (BS) during the OGTT, as compared with NT and EHT-N. EHT-R also had significantly higher FFA and TG than the other two groups, while there was no difference in FFA or TG between EHT-N and NT. TC and HDL-C were similar in the three groups. There was either a significant negative correlation, or a trend toward negative correlation, between M value and FFA (r= -0.50, p < 0.05) or TG (r= -0.24, p < 0.1). There were significant positive correlations between IRI-120 and FFA (r=0.35, p< 0.05) or TG (r=0.29, p< 0.05). There was a positive correlation (r= -0.36, p< 0.01) between sigma BS and FFA, while no other significant relation was found between sigma BS and serum lipids. In summary, (i) 33.3% of EHT were found to be insulin resistant, when insulin resistance was defined as M value < 145.0 mg/m2/min, i.e., mean -ISD of the M value of NT; (ii) these EHT-R had higher levels of BS, insulin, FFA, and TG than did NT and EHT-N; (iii) EHT-N showed no difference in the levels of BS, insulin, or lipid, as compared with NT; and (iv) the levels of FFA and of TG correlated negatively with insulin sensitivity and positively with the insulin level during the OGTT. These results suggest that disturbances of glucose and lipid metabolism in EHT may be related to both insulin resistance and compensatory hyperinsulinemia, and that EHT-R may have more risk factors for arteriosclerotic complications than EHT-N.

Blood Glucose↗
PubMed1998

Rheumatoid arthritis associated with renal amyloidosis and crescentic glomerulonephritis.

A 43-year-old woman with rheumatoid arthritis (RA), renal amyloidosis and crescentic glomerulonephritis had severe abdominal pain, melena and progressive renal failure. Autopsy findings revealed vasculitis of small and middle size of vessels and there was a deposition of amyloid in the small intestines. Although there were no findings of vasculitis in the kidney, amyloid deposition was noticed and 70-80% of glomeruli showed a crescentic formation. No immunological abnormality was found in glomeruli. Although the immunological mechanisms of crescentic glomerulonephritis were not necessarily eliminated, amyloid deposition may play a role in crescent formation.

Acute Kidney Injury↗
PubMed1998

[Involvement of glucose metabolism abnormalities and insulin resistance in atherosclerotic coronary artery disease: semiquantitative coronary angiography study].

Insulin resistance is known to be important in the aggravation of established coronary risk factors, but it is unclear whether insulin resistance might cause coronary artery disease as diabetes mellitus. To evaluate the relationship between insulin resistance and coronary atherosclerosis, the angiographic semiquantitative score of coronary atherosclerosis was investigated in 216 patients (175 males, 41 females) with coronary artery disease and the varying degrees of glucose metabolism including insulin resistance. Insulin resistance was estimated by plasma insulin level at 120 min after the 75g oral glucose tolerance test. Patients were divided into 3 groups according to the levels of glucose metabolism: 37 patients with treated diabetes mellitus, 48 with glucose intolerance and non-treated diabetes, and 131 with normal glucose tolerance. Multivessel disease was more frequently seen in the treated diabetes group (67.6%) than in the glucose intolerance and non-treated diabetes groups (43.8%) and in the normal glucose tolerance group (40.5%). The severity of coronary artery stenosis (8.5 +/- 3.9 vs 7.6 +/- 3.7 vs 6.6 +/- 3.7) and calcification (6.5 +/- 6.3 vs 3.3 +/- 3.3 vs 4.0 +/- 4.8) were significantly higher in the treated diabetes group than in other groups. Distal coronary lesions were significantly more frequent in the treated diabetes group (61.1% vs 17.6% vs 27.4%) than in other groups. Half of the patients in the normal glucose tolerance group had hyperinsulinemia. Multivessel disease was significantly more frequent in the insulin resistant subgroup than in the insulin non-resistant subgroup (59.4% vs 25.0%, p = 0.011). The severity of coronary artery stenosis was significantly higher in the insulin resistant subgroup than in the insulin non-resistant subgroup (8.6 +/- 3.9 vs 5.6 +/- 3.0, p < 0.001), but the severity of coronary artery calcification was not significant. Distal coronary lesions showed a tendency to increase in the insulin resistant subgroup (37.5% vs 12.0%, p = 0.081). These results suggest that insulin resistance is an important risk factor for coronary artery disease in patients with normal glucose tolerance, and is related to the severity and multiplicity of coronary atherosclerosis as in patients with diabetes.

Blood Glucose↗
PubMed1997

Role of the angiotensin II type 1 receptor in preconditioning against infarction.

OBJECTIVE: To assess the role of angiotensin II type 1 (AT1) receptor in the mechanism of limitation of infarct size by preconditioning. METHODS: Myocardial infarction was induced by 30 min coronary artery occlusion and 3 h reperfusion in the rabbit. The infarct size was determined by tetrazolium staining and expressed as a percentage of the area at risk (%ISAR). Rabbits were subjected to one of the following four treatments: no drug (i.e. control); administration of 1 mg/kg CV-11,974, a specific AT1 receptor antagonist, 20 min before ischemia; preconditioning with 5 min ischemia and then 5 min reperfusion; and administration of CV-11,974 plus preconditioning. RESULTS: It was confirmed that the same dose of CV-11,974 (i.e. 1 mg/kg) could block the pressor response to injection of 0.5 microgram/kg angiotensin II completely for 60 min. The %ISAR for the untreated control group was 45.1 +/- 3.9%, and administration of CV-11,974 alone did not modify the %ISAR (47.5 +/- 5.9%). The %ISAR for the group administered both CV-11,974 and subjected to preconditioning (30.4 +/- 3.5%) was modestly smaller than that for the controls, but was significantly larger than for the preconditioned group (12.0 +/- 1.8%). The angiotensin II level in arterial plasma did not differ before and after the 5 min preconditioning. It was shown with separate groups of rabbits that a modest protection conferred by preconditioning with 3 min ischemia was also attenuated by administration of CV-11,974 (%ISAR 28.4 +/- 4.3 with CV-11,974 versus 19.3 +/- 1.7% without CV-11,974, P < 0.05). CONCLUSION: These results suggest that activation of AT1 receptors by angiotensin II produced locally in the heart contributes to the limitation of infarct size by preconditioning.

Angiotensin II↗
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

Urinary kallikrein in Dahl-Iwai salt-sensitive and -resistant rats.

This study was designed to evaluate the differences between the renal kallikrein in newly established Dahl-Iwai rats under salt loading and that of Sprague-Dawley rats (SD). Urinary kallikrein quantity and activity was markedly lower in Dahl-Iwai rats than in SD even during the control period. Moreover, kallikrein quantity and activity in Dahl-Iwai salt-sensitive rats (SS) were clearly diminished in comparison with salt-resistant rats (SR). The kallikrein activity/ quantity ratio was also lower in SS and SR than in SD during the control period. After salt loading, systolic blood pressure increased only in SS. Kallikrein activity in SS and SR, and kallikrein quantity in SS were increased, whereas those in SD did not change. Although the kallikrein activity/quantity ratio in SR reached the same level in SD after salt loading, that in SS was lower throughout the experiment. These results suggest that Dahl-Iwai rats are less able hereditarily to produce renal kallikrein and that there may exist structurally abnormal kallikrein that may have a lower activity. Different kinetics of renal kallikrein between SS and SR by salt loading might be explained by kallikrein inhibitors or abnormal kallikrein or nonkallikrein kininogenase. These different kinetics of renal kallikrein may play some role on blood pressure elevation in SS.

Animals↗
PubMed1997

[Prostaglandin and kallikrein-kinin systems].

We reviewed the recent advances in the molecular characterization of prostanoid and bradykinin receptors. Prostanoids and bradykinin exert versatile actions in diverse tissues and cells through specific cell surface receptors. Molecular biological studies revealed the primary structure of eight types and subtypes of prostanoid receptors from various species. These include the thromboxane A2 receptor, prostacyclin receptor, prostaglandin (PG) F receptor, PGD receptor and four subtypes of PGE receptor (EP1, EP2, EP3 and EP4). There are four subtypes of bradykinin receptor (BK1, BK2, BK3 and BK4), but it is still unknown about the detail of BK3 and BK4. These results also have achieved the remarkable development in the field of human hypertension.

Animals↗
PubMed1997

Appropriate hematocrit levels of erythropoietin supplementary therapy in end-stage renal failure complicated by coronary artery disease.

OBJECTIVE: To investigate an appropriate hematocrit (Hct) for managing renal anemia complicated by angina pectoris at rest. DESIGN: Nonrandomized, retrospective and prospective observational study. SETTING: Sapporo Medical University Hospital, Sapporo, Japan. PATIENTS: Thirty-two anemic patients (aged 62 +/- 10 years, range 40 to 78) with rest angina in end-stage renal failure. INTERVENTIONS: Serial changes of exercise tolerance (estimated metabolic equivalents [METs] on stress electrocardiography produced by improvement of patients' Hct, using recombinant human erythropoietin (rHuEPO). Adverse effects, such as deteriorating systemic hypertension, were investigated with regard to the severity of coronary arteriographic findings (Leaman's score) and cardiac events within a six-month period. MAIN RESULTS: Higher Hct was clearly correlated with better estimated METs: when Hct was less than 20%, MET was 1.4 +/- 0.5; with 20% < or = Hct < 25% 2.1 +/- 1.4; with 25% < or = Hct < 30% 3.1 +/- 1.6; and with 30% < or = Hct < 35% 4.9 +/- 1.1. Patients with cardiac events (elective balloon angioplasty [n = 5], bypass surgery [n = 1], myocardial infarction [n = 2] and hospital death from congestive heart failure [n = 3]) had advanced coronary lesions compared with patients without coronary events (Leaman's score 15.9 +/- 9.3 versus 7.3 +/- 4.4, respectively, P < 0.01) and lower exercise capacity at 25% < or = Ht < 30% (estimated METs 2.4 +/- 1.2 versus 3.9 +/- 1.9, respectively, P < 0.05). Moreover, there was an inverse linear correlation between estimated METs and Leaman's score only when Hct was over 25%. In prospectively examined subjects (n = 16), Hct 35% or greater without systemic hypertension was obtained in only seven (44%), and no additional effect on exercise tolerance was expected when Hct was 35% or greater. CONCLUSIONS: Managing renal anemia with 30% < or = Hct < 35% with rHuEPO is considered an appropriate therapy in patients with end-stage renal failure complicated by rest angina.

Adult↗
PubMed1996

Captopril potentiates the myocardial infarct size-limiting effect of ischemic preconditioning through bradykinin B2 receptor activation.

OBJECTIVES: To investigate the role of kinin in preconditioning against infarction, the present study assessed the effect of captopril, a kininase II inhibitor, on preconditioning and arterial plasma kinin levels. BACKGROUND: Recent studies suggest a possible contribution of kinin to preconditioning against infarction. However, its role and the site of kinin production remain uncharacterized. METHODS: Six groups of rabbits (n = 6 to 13) underwent 30-min coronary occlusion and 3-h reperfusion. The infarct size and area at risk were determined by tetrazolium staining and fluorescent particles, respectively. Arterial blood was sampled under baseline conditions, before the 30-min ischemia and after reperfusion for radioimmunoassay of the kinin level. RESULTS: Infarct size expressed as a percentage of area at risk (%IS/AR) was 42.9 +/- 2.9% (mean +/- SEM) in the control group, 34.5 +/- 3.3% in the group preconditioned with 2 min of ischemia/5 min of reperfusion and 41.7 +/- 5.1% in the group given captopril (1 mg/kg body weight) alone before the 30-min ischemia. These %IS/AR values were not significantly different between the three groups. However, a combination of captopril and subsequent preconditioning with 2 min of ischemia markedly limited %IS/AR to 21.2 +/- 2.4%. This potentiation of 2 min of preconditioning by captopril was not observed when 2 micrograms/kg body weight of Hoe 140, a specific bradykinin B2 receptor antagonist, was administered before preconditioning (%IS/AR = 41.2 +/- 5.7%), whereas Hoe 140 alone did not modify infarct size (%IS/AR = 38.5 +/- 5.1%). Arterial plasma kinin levels were comparable between the control rabbits, the group given captopril alone and the group that received captopril plus 2 min of preconditioning at baseline (3.8 +/- 1.0, 6.3 +/- 1.9 and 5.2 +/- 1.7 pg/ml, respectively), and there was no significant change in kinin levels after the captopril injection or the combination of captopril plus 2 min of preconditioning. CONCLUSIONS: The present results indicate that captopril is capable of potentiating preconditioning without increasing the arterial kinin level and that the beneficial effect of captopril can be inhibited by Hoe 140. These findings support the hypothesis that kinin produced locally in the heart during preconditioning may contribute to the cardioprotective mechanism through bradykinin receptor activation.

Angiotensin-Converting Enzyme Inhibitors↗