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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of the cytosolic and mitochondrial redox state on the function and phosphorylation potential of working perfused rabbit hearts were studied. Hearts were perfused with glucose, while lactate, aminooxy-acetate (an inhibitor of the malate-aspartate shuttle), beta-hydroxybutyrate, and pyruvate were sequentially added to the perfusate to manipulate the cytosolic and mitochondrial NAD+/NADH ratio. The phosphorylation potential and product of ADP and P(i) were both found to be proportional to mitochondrial redox state. There was no overall relationship between cytosolic redox potential and the ATP/ADP x P(i) ratio, although at high mitochondrial NADH, there was a tendency for the states with more reduced cytoplasm to be associated with a lower phosphorylation potential. Cardiac output and dP/dt were decreased after 75 microM aminooxy-acetate was present for 15 min, and remained low when 0.5-1.0 mM beta-hydroxybutyrate was added, even though the beta-hydroxybutyrate period was characterized by both very low cytosolic NAD+/NADH and high mitochondrial NADH. Function returned to normal when the cytoplasm was oxidized by addition of 10 mM pyruvate, and although MVO2 rose from 4.0 +/- 0.4 to 5.0 +/- 0.5, this was not accompanied by statistical changes in either mitochondrial NADH or phosphorylation potential. Therefore, the cytosolic redox state may play a role in cardiac function, but has only a minor contribution to the regulation of the phosphorylation potential in the working perfused rabbit heart.
J Mol Cell Cardiol 1994 Dec
PMID:The relationship between phosphorylation potential and redox state in the isolated working rabbit heart. 773 Oct 48

An experimental model of myocardial ischemia/reperfusion injury was used to assess the cardioprotective effects of SC-52608, a low molecular weight superoxide dismutase mimetic. Langendorff perfused rabbit isolated hearts were subjected to 30 min of global ischemia followed by 45 min of reperfusion. Hearts perfused in the presence of 20 microM SC-52608 exhibited a decrease in the release of creatine kinase and intracellular potassium compared to hearts receiving vehicle (control). A progressive increase in left ventricular end-diastolic pressure developed upon reperfusion in all hearts, but was significantly greater in control hearts when compared to hearts treated with SC-52608 (P < 0.05). In addition, results obtained with a radiolabeled monoclonal antibody to the intracellular protein myosin, indicate an increased degree of irreversible damage in vehicle-treated hearts. Myocardial protection was not significant in an additional group of hearts treated with 10 microM SC-52608. The hemodynamic, biochemical, morphological, as well as the antimyosin binding data, demonstrate that pretreatment with SC-52608 protects the myocardium from damage associated with global ischemia and reperfusion. The mechanism by which SC-52608 mediates the observed protective effect is most likely related to its ability to scavenge superoxide.
J Mol Cell Cardiol 1994 Aug
PMID:Protective effects of the SOD-mimetic SC-52608 against ischemia/reperfusion damage in the rabbit isolated heart. 779 54

Metabolic fuel oxidation may be altered in left ventricular hypertrophy (LVH), but detailed characterizations are lacking. Although the spontaneously hypertensive rat (SHR) is a widely used experimental model of LVH, its myocardial fuel oxidation rates are unknown. The purpose of this study was to directly measure glucose and fatty acid (FA) oxidation in the SHR heart ex vivo under controlled loading conditions. Hearts from 15-week-old SHR and Sprague Dawley (SD) rats were perfused in a recirculating system and indices of cardiac performance were continuously monitored. The oxidation of glucose and palmitate were determined simultaneously at low and high workloads by the addition of U-14C-glucose and 9,10-3H-palmitate to the recirculating perfusate. The results demonstrate that FA oxidation of SHR hearts is profoundly suppressed (60-80%) relative to that of the normotensive SD strain, particularly at high workloads. Glucose oxidation is also moderately elevated, yielding a marked (four-to-five-fold) increase in the ratio of glucose/FA oxidation rates in the SHR hearts. Since more ATP is generated per mole of oxygen consumed when glucose is the fuel scource, these results are consistent with the hypothesis that a shift away from FA use toward glucose contributes to the preservation of energetic economy in stable, concentric LVH.
J Mol Cell Cardiol 1994 Oct
PMID:Altered glucose and fatty acid oxidation in hearts of the spontaneously hypertensive rat. 786 97

The effects of preconditioning, adenosine and dipyridamole in protecting the systolic and diastolic alterations of myocardial stunning in rabbit hearts were studied. Isovolumic left ventricular developed pressure (LVDP), and end diastolic pressure (LVEDP) were measured. The time constant of relaxation (T) was calculated. Isolated rabbit hearts were subject to 15 min of global ischemia (37 degrees C) followed by 30 min of reperfusion. LVDP and LVEDP stabilized to 55 +/- 5% and 320 +/- 28% of control values respectively (stunned group) T increased early in reperfusion (from 48.2 +/- 3.9 to 97.2 +/- 10 ms P < 0.05) but returned to control value late in reperfusion. When hearts were preconditioned by a single cycle of 5 min of ischemia LVDP and LVEDP stabilized at 89 +/- 3% and 162 +/- 34% of preischemic values respectively (P < 0.05 with respect to stunned group). The change in T was attenuated (62 +/- 6 ms at 5 min of reperfusion, P < 0.05 with respect to stunned group). Hearts treated either with adenosine (800 micrograms/min) or the nucleoside transport blocker dipyridamole (4 micrograms/min) previously to the ischemia, recovered their LVDP to 86 +/- 1% and 82 +/- 3% of preischemic values, respectively (P < 0.05 with respect to stunned group). Adenosine and dipyridamole also attenuated the increase in LVEDP (195 +/- 12% and 197 +/- 10% respectively, P < 0.05 with respect to stunned group).(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1994 Oct
PMID:Adenosine and dipyridamole mimic the effects of ischemic preconditioning. 786

The effects of beta and alpha-adrenergic stimulation in amphibian superfused hearts and ventricular strips were studied. Superfusion with 3 x 10(-8) M isoproterenol produced a positive inotropic effect, as detected by a 92 +/- 24% increase in the maximal rate of contraction (+T) and a positive lusitropic effect characterized by a decrease in both the ratio +T/-T (23 +/- 5%) and the half relaxation time (t1/2) (19 +/- 4%). The mechanical behavior induced by the beta-agonist was associated with an increase in the intracellular cAMP levels from control values of 173 +/- 19 to 329 +/- 28 nmol/mg wet tissue. Hearts superfused with 32P in the presence of isoproterenol showed a significant increase in Tn 1 phosphorylation (from 151 +/- 13 to 240 +/- 44 pmol 32P/mg MF protein) without consistent changes in phosphorylation of C-protein. In sarcoplasmic reticulum membrane vesicles, no phospholamban phosphorylation was detected either by beta-adrenergic stimulation of superfused hearts or when phosphorylation conditions were optimized by direct treatment of the vesicles with cAMP-dependent protein kinase (PKA) and [gamma 32P] ATP. The effect of alpha-adrenergic stimulation on ventricular strips was studied at 30 and 22 degrees C. At 30 degrees C, the effects of 10(-5) to 10(-4) M phenylephrine on myocardial contraction and relaxation were diminished to non significant levels by addition of propranolol. At 22 degrees C, blockage with propranolol left a remanent positive inotropic effect (10% of the total effect of phenylephrine) and changed the phenylephrine-induced positive lusitropic effect into a negative lusitropic action.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1994 Dec 21
PMID:Lusitropic effects of alpha- and beta-adrenergic stimulation in amphibian heart. 789 75

This study was undertaken to investigate whether prior antioxidant supplementation had a beneficial effect on subsequent myocardial ischemic/reperfusion injury and whether addition of ascorbate during ischemia/reperfusion had any effect. Supplementation with antioxidants resulted in elevated concentrations of myocardial alpha-tocopherol, but not of ascorbate. Combined supplementation with alpha-tocopherol, beta-carotene and ascorbic acid gave the highest myocardial alpha-tocopherol concentration. Hearts of rats supplemented with antioxidants was partially protected to ischemia/reperfusion as indicated by the mitochondrial function. However, addition of ascorbate during ischemia/reperfusion nullified this protective effect.
Res Commun Mol Pathol Pharmacol 1994 Jul
PMID:Antioxidant supplementation partially protects against myocardial mitochondrial ischemia/reperfusion injury, but ascorbate in the perfusate prevented the beneficial effect. 795 93

The coronary vascular effect of atrial natriuretic peptide is controversial: Coronary vasodilator as well as constrictor effects have been reported. The controversy may originate from interference of atrial natriuretic peptide with the renin-angiotensin system and/or tachyphylaxis of the effect of atrial natriuretic peptide. The effect of alpha-human atrial natriuretic peptide bolus application on changes of coronary flow was examined in the isolated, constant-pressure perfused rat heart. Six groups were considered: (1) control group; groups in which the renin-angiotensin system was modulated by pretreatment with continuous infusion of: (2) angiotensin II, (3) the angiotensin converting enzyme inhibitor captopril (4) the angiotensin II receptor blocker saralasin; and groups in which tachyphylaxis was examined by pretreatment with ANP, (5) as continuous infusion and (6) as bolus application. First, in control hearts, dose-response curves were obtained for single ANP dosages of 1-100 nmol. The effect of high dosages (40 and 100 nmol) was biphasic, with an initial vasodilator and subsequent long-lasting vasoconstrictor component. Hearts in which coronary flow was reduced by approximately 18% through continuous angiotensin II infusion showed an enhanced early vasodilator response after ANP administration, whereas the vasoconstrictor effect was no longer observable. Angiotensin converting enzyme inhibition and angiotensin II receptor blockade reduced the vasodilator effect of ANP. In addition, saralasin nearly abolished ANP-induced vasoconstriction, whereas vasoconstriction was unaltered by pretreatment with captopril. Captopril or saralasin alone did not change coronary flow, heart rate and left ventricular developed pressure. In groups (5) and (6). ANP bolus application showed significantly reduced vasomotor activity. We conclude that in the isolated rat heart. ANP has a biphasic effect with early vasodilation and late vasoconstriction. Both effects can be modulated by inhibition of the renin-angiotensin system at different levels indicating that vasomotor ANP effects result from interaction of ANP with the local renin-angiotensin system. ANP effects can be markedly reduced by tachyphylaxis.
J Mol Cell Cardiol 1994 Apr
PMID:Interrelation of coronary effects of atrial natriuretic peptide and the renin-angiotensin system in the isolated perfused rat heart. 807 8

We evaluated, firstly, the sensitivity to cardiac ischemic ATP breakdown during the development of hypertension and cardiac hypertrophy in Spontaneously Hypertensive Rats (SHR) v Wistar Kyoto (WKY) controls, and secondly, the effects of short-term (8 days) and prolonged (3 months) antihypertensive treatment with the angiotensin converting enzyme inhibitor enalapril on hypertrophy and sensitivity to global ischemia. In isolated perfused hearts, ischemia was induced by a stepwise lowering of the perfusion pressure and the appearance of the ATP breakdown products (purines) in the coronary effluent was assessed as a measure of ischemia. Hearts from 2.5- and 4-month-old SHR started to release purines at a higher perfusion pressure than hearts of WKY, associated with a higher maximum concentration in the coronary effluent. This increased ischemic ATP breakdown in 2.5- and 4-month-old SHR could be attributed to a decreased flow at a given perfusion pressure, because of a two-fold increase in coronary vascular resistance (CVR). In contrast, the maximal purine concentration in the coronary effluent in hearts of 7-month-old SHR was reduced compared to the younger SHR and only slightly higher than 7-month-old WKY, despite a persistent increase in CVR. Enalapril normalized the blood pressure, but only prolonged treatment, significantly prevented and regressed cardiac hypertrophy, and reduced CVR. Whereas enalapril did not influence ATP breakdown in WKY, in SHR both short- and long-term treatment normalized it to the pattern observed in WKY. We conclude that during the early phase of cardiac hypertrophy the hearts of SHR become more sensitive to ischemic ATP breakdown solely because of an increase in CVR, whereas during the established hypertrophic phase, the hearts appear to adapt metabolically, resulting in normalized purine release. Enalapril normalized the transient increase in sensitivity to ischemic ATP breakdown during the development of hypertension in SHR, independent of effects on cardiac hypertrophy, apparently by improving coronary flow at low perfusion pressures.
J Mol Cell Cardiol 1994 May
PMID:Age-related increase in sensitivity for ischemic ATP breakdown in hypertrophic hearts of SHR normalized by enalapril. 807 19

Cardiac proenkephalin (PENK) mRNA, methionine-enkephalin (ME) and leucine-enkephalin (LE) were determined from 2 days of age through senescence in Fisher 344 rats. Tissues were collected at 2 days, 2 weeks, 1, 2, 3, 7, 19, and either 22 or 27 months of age. Hearts were dissected, extracted and assayed for ME and LE by radioimmunoassay (RIA) or for PENK mRNA by Northern blot analysis with a cDNA probe. Relative left ventricular (LV) PENK mRNA was low in 2 day animals and increased slowly between 2 weeks and 3 months of age. LV PENK mRNA then rose five to six-fold between 3 and 27 months of age. LV ME measurements were high in neonatal animals, declined to a nadir during development and then rose again as the animals matured and advanced in age. The pattern for right ventricular (RV) ME was similar. Atrial ME, also high at 2 days, declined thereafter and remained low. LE measurements in LV, RV and the atria followed patterns similar to those described for ME. To evaluate for peptides contributed by cardiac nerves, 3, 7 and 22-month-old animals were acutely sympathectomized for 24 h with 6-hydroxydopamine. No decline in LV ME and LE was observed in the 6-hydroxydopamine treated animals. These data suggest several conclusions regarding myocardial enkephalinergic systems: (a) tissue enkephalin and PENK mRNA increase with advancing age, (b) tissue enkephalins may not strictly correlate with the relative abundance of PENK mRNA, and (c) most myocardial enkephalins are non-adrenergic in origin. The age-associated patterns in both PENK mRNA, ME and LE suggest that physiological, maturational or behavioral events between 3 and 7 months of age initiate the up-regulation and subsequent expansion of cardiac enkephalinergic systems.
J Mol Cell Cardiol 1994 Jun
PMID:Aging, cardiac proenkephalin mRNA and enkephalin peptides in the Fisher 344 rat. 808 51

Adventitious redox-active metals in Krebs-Henseleit buffer exhibit a significant enhancement of damage to isolated rat hearts. Using atomic absorption spectroscopy, it was determined that Krebs-Henseleit buffer contains substantial amounts of contaminating iron and copper. Significant copper contamination was found in ACS Reagent grade sodium chloride and sodium bicarbonate; iron contamination in sodium chloride, potassium chloride, sodium bicarbonate, and calcium chloride. Chelating resin treatment of individual reagents was found to decrease copper content of Krebs-Henseleit buffer from 0.32 to 0.17 microM. Using salicylate as a probe for .OH formation, it was determined that considerable amounts of this radical are formed when 0.25 mM ascorbate is added to the buffer indicating significant metal-catalysed autoxidation. Isolated rat hearts, perfused with non-chelexed Krebs-Henseleit buffer plus 0.25 mM ascorbate for 60 min, sustained moderate injury with developed systolic pressure, +dP/dtmax and -dP/dtmax decreased by 30 to 35% by the end of experiment. Hearts perfused with chelating resin-treated Krebs-Henseleit buffer sustained no significant injury within the same time frame. Furthermore, it was observed that hearts perfused with non-chelexed Krebs-Henseleit buffer accumulate significant amounts of copper depending on the amount of contamination and length of perfusion. Significant effects on post-ischemic end diastolic pressure were observed in hearts perfused with a Krebs-Henseleit buffer subsequently found to be contaminated with high levels of copper. These results clearly demonstrate that adventitious redox-active transition metals may be a confounding factor in experimental results. Further, it is recommended that all perfusion media be routinely examined for adventitious metals and treated if deemed necessary.
J Mol Cell Cardiol 1994 Jun
PMID:Adventitious redox-active metals in Krebs-Henseleit buffer can contribute to Langendorff heart experimental results. 852 67


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