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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 31 (2004), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Changes in [Ca2+]i across the cell membrane and/or the sarcoplasmic reticulum regulate endothelial nitric oxide (NO) synthase activity.2. In the present study, we investigated the effect of ouabain, a specific inhibitor of Na+/K+-ATPase, on NO release and [Ca2+]i movements in cultured rat aortic endothelial cells (RAEC) by monitoring NO production continuously using an NO-specific real-time sensor and by measuring the change in [Ca2+]i using a fluorescence microscopic imaging technique with high-speed wavelength switching. The t½ (half-time of the decline of [Ca2+]i to basal levels after stimulation with 10 µmol/L bradykinin) was used as an index of [Ca2+]i extrusion.3. A very low concentration of ouabain (10 nmol/L) did not increase the peak of NO production, but decreased the decay of NO release and, accordingly, increased integral NO production by the maximal dose–response concentration induced by bradykinin. The same dose of ouabain affected [Ca2+]i movements across the cell membrane and/or sarcoplasmic reticulum induced by bradykinin with a time-course similar to that of NO release. Moreover, the t½ was significantly increased.4. Pretreatment of RAEC with Na+-free solution, an inhibitor of the Na+/Ca2+ exchanger, and nickel chloride hexahydrate prevented the effects induced by bradykinin and ouabain.5. These observations using real-time recording indicate that a small amount of ouabain contributes to the bradykinin-stimulated increase of NO production through inhibition of plasma membrane Na+/K+-ATPase activity and an increase in intracellular Na+ concentrations. The membrane was then depolarized, leading to a decline in the bradykinin-stimulated increase in [Ca2+]i by forward mode Na+/Ca2+ exchange to prolong the Ca2+ signal time.6. From these results, we suggest that nanomolar levels of ouabain modulate [Ca2+]i movements and NO production in RAEC.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Melbourne, Australia : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 26 (1999), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Regional haemodynamic alterations caused by hypertonic NaCl solution (Hi-Salt; 10%, 10 μL) injected intracerebroventricularly (i.c.v.) were investigated by using radioactive microspheres in anaesthetized rats.2. Intracerebroventricular injections of Hi-Salt increased regional vascular resistance of visceral organs, including the kidney, and elevated plasma levels of vasopressin.3. Intracerebroventricular pretreatment with TCV-11974 (50 μg/10 μL/nat), an angiotensin AT1 receptor antagonist, attenuated the pressor response and vasopressin release to subsequently injected Hi-Salt, but did not affect regional haemodynamic effects of i.c.v. Hi-Salt on vascular resistance.4. In contrast, i.c.v. pretreatment with atrial natriuretic polypeptide (ANP) or type-C natriuretic polypeptide (CNP) almost completely abolished the haemodynamic changes and vasopressin release caused by i.c.v. Hi-Salt.5. The present findings indicate that a natriuretic family in the brain may be involved to a great degree in the central regulation of salt-induced hypertension in rats, while brain angiotensin II is likely to participate only in vasopressin release.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Fibronectins (FN) are believed to have a role in haemorheological perturbation associated with tissue damage. Fibronectins exist in two antigenically related forms, plasma (p) and cellular fibronectin, which has the extra domain sequences A (EDA) or B (EDB). The present study was designed to determine changes in plasma p-FN and EDA + FN under different types of surgical stress.2. Sixty-two patients were divided into three groups: (i) group A, 33 patients undergoing hepato–pancreato–biliary surgery; (ii) group B, 19 patients undergoing laparoscopic cholecystectomy; and (iii) group C, 10 patients with postoperative complications. Plasma FN and EDA + FN levels were measured in these patients undergoing different types of surgical operation and either with or without liver cirrhosis using an enzyme-linked immunosorbent assay.3. After surgery, a significant decrease in p-FN levels and a significant increase in EDA + FN levels was observed in all patient groups compared with pre-operative levels. The duration of increased EDA + FN levels, but not p-FN levels, in group A patients was significantly longer than in group B patients. Although changes in p-FN levels between patients with and without liver cirrhosis were significantly different, there were no significant differences in the EDA + FN levels between these two patient groups.4. In conclusion, EDA + FN and p-FN levels were found to exhibit opposite responses to surgical stress. Furthermore, with greater surgical stress, greater increases in EDA + FN levels were seen. The presence of liver cirrhosis had no significant effect on EDA + FN levels during the perioperative period; however, p-FN levels were significantly affected.5. Thus, it is suggested that plasma EDA + FN levels reflect the magnitude of surgical stress more closely than do p-FN levels.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 18 (1991), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The effects of sodium-loading on releases of endogenous digitalis-like substance were investigated by measuring digoxin-like immunoreactivity (DLI) during intravenous infusions of isotonic (0.15 mol/L) and hypertonic (1 mol/L) saline in anaesthetized rats. Plasma DLI was measured after death by a digoxin-radioimmunoassay.2. The infusion of isotonic saline and hypertonic saline elevated the central venous pressure to similar levels. The plasma DLI concentration in both the infused groups rose significantly compared with that in the control rat not receiving the intravenous infusion.3. The difference in the hypothalamic concentrations of DLI was not significant among the three groups, however, there was a significant inverse relationship between the plasma and hypothalamic concentrations of DLI.4. Results indicate that the central venous pressure, but not sodium concentration, is essentially involved in the release of DLI, possibly from the hypothalamus.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 17 (1990), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The role of cerebral insulin or insulin-like immunoreactive substance (ILI) on arginine–vasopressin (AVP) release using rats was investigated. Feeding rats with a high salt diet for 4 weeks significantly decreased the contents of ILI in both the hypothalamus and pituitary gland. Intracerebroventricular infusions of insulin (4 and 40 μg/min for 30 min) increased plasma AVP concentrations dose-dependently without hypoglycaemia, but decreased hypothalamic and pituitary contents of AVP.2. These results indicate that ILI in the brain may play a role in the secretion of AVP, and that this mechanism could be operated to control a water–sodium balance.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Diabetes mellitus is significantly associated with the occurrence of congestive heart failure in end-stage renal disease patients undergoing maintenance haemodialysis. In the present study, we asked whether the left ventricular remodelling against sustained pressure and/or volume overload to the left ventricle may be different between diabetic and non-diabetic haemodialysis patients.2. Left ventricular parameters, including left ventricular mass index (LVMI), interventricular septal wall thickness (IVST) and relative left ventricular wall thickness (rLVWT), were assessed in 486 patients receiving maintenance haemodialysis (145 diabetic and 341 non-diabetic patients) using transthoracic echocardiography. Plasma concentrations of B-type natriuretic peptide (BNP), measured with an immunoradiometric assay, were used as a humoral parameter indicating left ventricular wall stress.3. In non-diabetic patients, the plasma BNP concentration correlated with LVMI (r = 0.245; P = 0.0001), IVST (r = 0.250; P = 0.0001) and rLVWT (r = 0.149; P = 0.006). Furthermore, LVMI was correlated with mean blood pressure and pulse pressure and IVST and rLVWT were correlated with pulse pressure.4. In contrast, none of the measured factors was correlated with LVMI and IVST in diabetic patients. Plasma BNP concentrations were positively correlated with end-systolic and end-diastolic left intraventricular dimensions and were inversely correlated with rLVWT and left ventricular fractional shortening in diabetic patients, but not in non-diabetic patients.5. In conclusion, a sustained increase in left ventricular wall stress is likely to elicit eccentric left ventricular remodelling in diabetic haemodialysis patients, whereas it causes concentric left ventricular remodelling in non-diabetic haemodialysis patients. This difference in left ventricular remodelling against left ventricular overload may be associated with the high incidence of congestive heart failure in diabetic haemodialysis patients.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Melbourne, Australia : Blackwell Science Asia Pty. Ltd.
    Clinical and experimental pharmacology and physiology 29 (2002), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The effect of vasodilatory β-adrenoceptor blockers on regional blood flow in the major organs of anaesthetized rats was investigated using radioactive microspheres. The administration of propranolol and saline was used as a control.2. Intravenous injections of carvedilol (2 mg/rat), celiprolol (20 mg/rat) and bopindolol (1 mg/rat) equally decreased systemic blood pressure (SBP) by approximately 20 mmHg, whereas propranolol (1 mg/rat) decreased SBP only slightly but not significantly.3. Heart rate was significantly decreased by carvedilol, celiprolol, bopindolol and propranolol.4. Coronary blood flow was markedly increased by carvedilol, but not by the other three drugs.5. Cardiac output tended to decrease following the administration of all four drugs.6. Total peripheral vascular resistance was not significantly affected by carvedilol, celiprolol and bopindolol, but was markedly increased following propranolol.7. Renal blood flow was markedly increased by carvedilol.8. Blood flow in the brown fat was markedly increased by carvedilol and bopindolol, but not by celiprolol and propranolol.9. These findings indicate that the newer vasodilatory beta-blockers, such as carvedilol and bopindolol, have a beneficial effect on the regional circulation in contrast with the classical beta-blocker propranolol.10. The regional haemodynamic effects observed in the present study following intravenous injection of the beta-blockers may help explain the clinical experience that vasodilatory beta-blockers increase insulin sensitivity and decrease mortality in patients with congestive heart failure.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Melbourne, Australia : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 27 (2000), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Although hepatic function is well known to deteriorate following bacterial infection, the underlying mechanisms remain poorly understood. We have previously reported that nitric oxide (NO) radical leads to a decrease in the ketone body ratio (KBR) and in ATP content due to the inhibition of mitochondrial electron transport in primary cultured rat hepatocytes.2. To evaluate the effects of NO radical on the liver in patients with postoperative sepsis, we analysed both the stable end-product of nitric oxide radical (NOx) as well as the arterial KBR (AKBR), which reflects liver tissue NAD+/NADH.3. Twenty patients who had undergone general abdominal surgery and who developed postoperative sepsis were divided into two groups: (i) surviving; and (ii) non-surviving. Blood samples were collected before the development of postoperative sepsis and every 3 days until the patient either died or was discharged from hospital.4. Plasma NOx levels in seven patients who subsequently died became progressively higher than those in the 13 surviving patients over the clinical course of postoperative sepsis.5. In the non-surviving group, the AKBR was significantly lower than in surviving patients, indicating impaired hepatic function. In contrast, plasma NOx levels in non-surviving patients were significantly higher than in surviving patients.6. Decreases in AKBR to levels below 0.7 in non-surviving patients followed high NOx levels. Moreover, plasma NOx levels were closely correlated with the AKBR, indicating that NO radical is associated with mitochondrial dysfunction in the liver.7. It is likely that the overproduction of NO radical plays an important role in causing fatal metabolic disorders in patients with postoperative sepsis.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Melbourne, Australia : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 27 (2000), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The aim of the present study was to investigate whether long-term oral administration of eicosapentaenoic acid increases nitric oxide (NO) production and affects cardiac sympathetic activity in rats with diabetes mellitus.2. We measured changes in urinary excretion of NO3–, a stable NO metabolite, and cardiac noradrenaline (NA) concentrations in non-diabetic rats and streptozotocin-induced diabetic rats treated with either ethyl icosapentate (EPA-E; 100 mg/kg per day; n = 10), a purified ethyl esterification product of eicosapentaenoic acid, or vehicle (distilled water; n = 10) for 6 weeks. The effects of NG-nitro- L-arginine ( L-NNA), a NO synthase inhibitor, on urinary NO3– excretion and cardiac NA concentrations were also investigated in diabetic rats treated with EPA-E.3. Urinary NO3– excretion was higher at weeks 5 and 6 in diabetic rats treated with EPA-E than in diabetic rats treated with vehicle (week 5: 120±8 vs 51±11 μmol/g per day, respectively (P 〈 0.01); week 6: 279±83 vs 73±9 μmol/g per day, respectively (P 〈 0.01)). Cardiac NA concentrations were higher in diabetic rats than in non-diabetic rats and were decreased in the left atrium and both ventricles in diabetic rats treated with EPA-E compared with control. Systemic administration of L-NNA abolished the increase in urinary excretion of NO3– and the decrease in cardiac NA concentrations in diabetic rats treated with EPA-E.4. Long-term oral administration of EPA-E may stimulate NO production and increased NO is likely to play a role in inhibiting enhanced cardiac sympathetic activity in diabetic rats.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The stirnulatory effects of isoproterenol on the L-type Ca2+ current (Ic.) were compared between the control (WKY) and hypertensive (SHR) rat heart cells, using the patch-clamp method.2. The current density and the shape of the current-voltage relationship for Ic. were not different between the two groups. However, the maximal percentage increase in response to isoproterenol was smaller in SHR (+ 91% in SHR and + 81% in WKY), and the ED50 was significantly higher in SHR (0.081 μmol/L in SHR and 0.020 μmol/L in WKY). IBMX, a potent phosphodiesterase inhibitor, significantly increased the isoproterenol-stimulated Ica in SHR, but not in WKY. These results suggest an impaired CAMP production in SHR heart cells.
    Type of Medium: Electronic Resource
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