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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Free Radical Biology and Medicine 9 (1990), S. 101 
    ISSN: 0891-5849
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 23 (1996), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. In the present study, using the euglycaemic hyperinsulinaemic glucose clamp technique, we investigated the effects of hyperinsulinaemia on sodium-water metabolism and the pressor system in obesity, both of which have been reported to be closely associated with insulin resistance and/or hyperinsulinaemia.2. Sixteen obese young subjects and 24 non-obese young subjects who were all normotensives, participated in this study. The 2h euglycaemic hyperinsulinaemic glucose clamp was performed in a fasting state. The mean glucose infusion rate needed to maintain a fasting blood sugar level (FBS) during the last 30 min of the clamp was used as an indicator of insulin sensitivity (M-value). Before and after the clamp, the following parameters were measured: creatinine clearance (Ccr); urinary excretion of sodium (UNaV); fractional excretion of sodium (FENa); plasma renin activity (PRA); plasma aldosterone concentration (PAC) and plasma noradrenaline concentration (PNA).3. The M-value was significantly lower in obese subjects compared with non-obese subjects, although FBS and fasting immunoreactive insulin levels were similar in both groups. UNaV and FENa fell only in obese subjects during the clamp, while Ccr showed no significant change in either group. PNA and PRA increased significantly and PAC tended to increase in both groups.4. These results suggest that obese subjects have insulin resistance with respect to glucose metabolism, but that urinary sodium excretion and the pressor system remain insulin-sensitive; the sensitivity of the sodium retaining action to hyperinsulinaemia was actually higher in obese subjects than in non-obese subjects. Therefore, if compensatory endogenous hyperinsulinaemia was raised by insulin resistance, these two factors may lead to chronic sodium retention and pressor system stimulation and, in turn, to hypertension in obesity.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0022-2828
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0022-2828
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0022-2828
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0022-2828
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2013
    Keywords: Hyperosmolality ; ANP ; cGMP ; Inner medullary collecting duct cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study was undertaken to explore the acute effect of hyperosmolality on the response of cultured rat inner medullary collecting duct (IMCD) cells to atrial natriuretic peptide (ANP). In contrast to the stimulatory effect of chronic incubation (12 h) in hypertonic medium, it was found that short-term incubation (〈 2 h) reversibly suppressed the ANP-dependent cyclic guanosine monophosphate (cGMP) production. Urea, NaCl and mannitol were equi-potent as the osmolyte in suppressing the ANP-dependent cGMP production. Receptor binding assay revealed that hyperosmolality induced a rapid and marked reduction of the maximum binding (B max) of ANP without a significant change of the dissociation constant (K d). Pretreatment with protein kinase C inhibitors (calphostin-C, staurosporin) or with cytoskeleton modulators (cytochalasin-B, colchicine) did not affect the inhibitory effect of hyperosmolality. In conclusion, acute hypertonicity inhibited the ANP-induced cGMP production in contrast to chronic hypertonicity, and reduction of the number of ANP binding sites was considered to be a mechanism responsible for the inhibitory effect of hypertonicity.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1435-1803
    Keywords: Adenosine ; bradykinin ; microdialysis ; myocardial infarction ; rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Preconditioning is known to decelerate degradation of the tissue adenine nucleotides during ischemia and to delay ischemic myocardial necrosis. However, it is not known whether these two phenomena are related. To obtain an insight into this question, the present study examined whether adenosine and B2 receptor antagonists, which block the infarct size-limiting effect of preconditioning, modify the interstitial purine levels during preconditioning and subsequent sustained ischemia. In pentobarbital anesthetized open-chest rabbits, a microdialysis probe was placed in the territory of a branch of the left coronary artery, and perfused with Ringer solution. Preconditioning was performed with 5 min ischemia/5 min reperfusion. Dialysate adenosine and inosine were elevated from the baseline values of 0.064±0.011 and 0.329±0.044μM to 0.189±0.069 and 4.106±1.451 μM, respectively during preconditioning, but their elevation during a subsequent 20 min of ischemia was significantly lower compared with that in the non-preconditioned myocardium. This suppression of the purine accumulation during ischemia by preconditioning was not abolished by 2 μg/kg of Hoe 140, a specific B2 receptor antagonist, or by 10 mg/kg of 8-phenyltheophylline, a non-selective adenosine receptor antagonist. Since the doses of Hoe 140 and 8-phenyltheophylline are sufficient to block the infarct size-limiting effect of preconditioning, the present results suggest that there is a dissociation between the suppression of adenine nucleotide degradation during ischemia by preconditioning and the enhancement of myocardial resistance against infarction. Thus, it is unlikely that a reduction of adenine nucleotide utilization by preconditioning is sufficient to protect the myocardium against ischemic necrosis.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1435-1803
    Keywords: Preconditioning ; myocardial stunning ; dobutamine ; infarct size ; rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Although previous studies have shown that preconditioning cannot be explained by concurrent myocardial stunning alone, it remains unclear whether reduction of contractile function by preconditioning ischemia is required for its cardioprotective effect. The present study examined whether preconditioning occurs in the absence of regional contractile dysfunction. In the first series of experiments, rabbits received two cycles of 2-min coronary occlusion separated by 5-min reperfusion, with or without dobutamine infusion (10 μg/kg/min, i.v.) commencing before the onset of ischemia. Regional thickening fraction measured by epicardial Doppler sensor was 72.8±4.7% of baseline (mean±SEM) in the untreated group and 102.9±3.1% in the dobutamine group at the end of the second cycle of ischemia/reperfusion. In the second series of the study, four groups of rabbits underwent 30-min coronary occlusion and reperfusion. The control group was untreated, and the PC group was preconditioned with two cycles of 2-min ischemia/5-min reperfusion before the 30-min ischemia. The PC-DOB group received both preconditioning and dobutamine infusion (10 μg/kg/min, i.v.), which was started 5 min before the preconditioning and continued for 19 min. The DOB group was given dobutamine infusion like the PC-DOB group, but was not preconditioned. After 72-h reperfusion, infarct size and area at risk were determined by histology and fluorescent particles, respectively. Infarct sizes in the PC and PC-DOB groups (25.0±3.4% and 22.7±3.3% of area at risk, respectively) were significantly smaller than that in the control group (48.2±2.6%). In the DOB groups, infarct size (43.5±4.0%) was similar to the control value. Infusion of dobutamine at a dose sufficient to abolish the contractile dysfunction which would have been induced by ischemic preconditioning did not attenuate the infarct size-limiting effect of preconditioning. Thus, it is unlikely that reduction of contractile function plays a permissive role in the appearance of the cardioprotective effect of preconditioning.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1435-1803
    Keywords: ATP ; myocardial stunning ; rabbit ; verapamil ; xanthine oxidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The role of free radicals and the protective action of calcium antagonists have been established in myocardial stunning in canine hearts, which contain a considerable level of xanthine oxidase, a free radical producing enzyme. However, myocardial stunning in hearts which lack xanthine oxidase and its modification by calcium antagonistsin vivo remain uncharacterized. The present study examined this issue using open-chest anesthetized rabbits. Myocardial stunning was induced by a 10-min coronary occlusion and reperfusion. Regional systolic thickening fraction (TF) was determined using an epicardial Doppler sensor, together with other hemodynamic parameters. In untreated control rabbits, recovery of TF from the 10 min transient ischemia was 43±3% of the baseline at 30 min after reperfusion. Administration of verapamil (200 μg/kg bolus plus 40 μg/kg/min), which was started before the onset of ischemia and continued until 20 min after reperfusion, significantly improved the recovery of TF to 74±6% (p〈0.05). A similar improvement in post-ischemic contractile function (TF=77±10%) was observed when verapamil was injected at the same rate, but the infusion was discontinued 1 min after the coronary occlusion. Myocardial ATP depletion after the 10 min ischemia was significantly less in the verapamil-pretreated rabbits compared with untreated controls (10.1±1.0 vs 6.2±0.7 μmol/g dry wt., p〈0.05). The difference in TF between the rabbits with and without verapamil treatment could not be explained by afterload reduction. When verapamil (100 μg/kg bolus plus 20 μg/kg/min) was given during the reperfusion period alone, TF recovery was poorer (TF=22±8%) than the control value. Thus, it was concluded that verapamil attenuates myocardial stunning in the hearts with trace levels of xanthine oxidase, and that the beneficial effect is achieved only by pretreatment, not by post-ischemic treatment with verapamil.
    Type of Medium: Electronic Resource
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