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

Hearts from untreated or enalapril-treated piglets were used to measure rates of ribosome formation and total protein synthesis during perfusion as modified Langendorff preparations. Pretreatment of newborn piglets with enalapril maleate (5 mg, once daily for 3 days) resulted in a decreased rate of growth of the left ventricle. Addition of 1 microM angiotensin II to the perfusate had no effect on in vitro ribosome formation or protein synthesis in either the right or left ventricle of hearts from untreated or enalapril-treated piglets. Angiotensin II receptor number or affinity in the left ventricle was not decreased by enalapril treatment. In contrast, addition of combinations of 1 microM norepinephrine and 1 microM propranolol or 1 microM phenylephrine and 1 microM propranolol to the perfusate restored the rate of ribosome formation in the left ventricle of hearts from enalapril-treated piglets to that observed in the left ventricle of hearts from untreated piglets. Prazosin (100 nM) blocked the stimulatory effect of either norepinephrine or phenylephrine on ribosome formation in the left ventricle. Binding of [3H] prazosin to membranes from the left ventricle was unaltered by pretreatment of the piglet with enalapril maleate. Pretreatment of piglets with prazosin (1 mg, twice daily for 3 days) resulted in a small but significant decrease in mean arterial pressure as well as the rate of left ventricular growth. Pretreatment of piglets with hydralazine (10 mg, twice daily for 3 days) significantly reduced mean arterial pressure but did not alter left ventricular growth. These results support a role for alpha 1-adrenergic receptor stimulation in the regulation of neonatal cardiac growth.
J Mol Cell Cardiol 1993 Apr
PMID:Alpha-adrenergic receptor agonists stimulate ribosome formation in hearts from enalapril-treated piglets. 810 80

The importance of the Na+/K+/Cl- co-transport system of the rat myocardial sarcolemma was studied under hypothermic ischemia by investigating the effect of the co-transport blockers furosemide and bumetanide on the sodium influx into the myocardium. The intracellular Na+ accumulation during hypothermic ischemia was followed by 23Na-NMR. For this purpose the shift reagent [Dy(TTHA)3-] (SR) was added to the Krebs-Henseleit (KH) perfusion solution. The same solution was also present during the hypothermic preservation. A significant reduction in the intracellular Na+ accumulation after 12 h was found when 100 microM furosemide was present during the perfusion and preservation periods. The intracellular Na+ levels returned to the pre-ischemic values after 1 h of reperfusion with KH in both the treated and control groups. Dose-response studies have indicated that 1-100 microM furosemide or 0.1 microM bumetanide added to the KH-SR solution reduced the Na+ influx significantly over 4 h of hypothermic ischemia. No statistically significant effect was found with furosemide concentration of 0.1 microM or with bumetanide concentrations higher or lower than 0.1 microM. 31P-NMR measurements showed no effect of the 100 microM furosemide on the intracellular ATP, the sum of inorganic phosphate and phosphomonoester, or pH levels over 4 h or after 12 h of hypothermic ischemia. Hearts treated with KH containing 100 microM furosemide showed, significantly higher functional recovery after 12 h of hypothermic ischemia than hearts treated only with KH. This study strongly indicates the existence of the Na+/K+/Cl- co-transport system in the intact rat heart sarcolemma, and its major role in sodium influx during hypothermic ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1993 Dec
PMID:Inhibition of sodium influx and improved preservation of rat hearts during hypothermic ischemia by furosemide and bumetanide: a 23Na- and 31P-NMR study. 815 60

Using a paced Lagendorff-perfused rabbit heart paradigm, we investigated the role of protein kinase C (PKC) in the development of ventricular fibrillation (VF) in hearts subjected to hypoxia (12 min) and re-oxygenation (40 min). We studied the effect of putative activators and inhibitors of PKC on the incidence of VF. Hearts exposed to 4 beta-phorbol,12,13-dibutyrate (PDBu), isophorbol or the membrane permeant diacylglycerol analog, 1-oleoyl-2-acetyl-rac-glycerol (OAG), during the prehypoxic phase had an increased incidence of VF during the hypoxic and reoxygenation periods. The incidence of VF was 90%, 83% and 75% in hearts exposed to PDBu, isophorbol and OAG, respectively (P < 0.05 vs control). Perfusion of hearts with PDBu was associated with a significant increase in the membrane fraction of cardiac PKC activity. In the presence of the inactive phorbol ester 4 alpha-phorbol didecanoate, the incidence of VF was 17% (P > 0.05 vs control). PKC activators were profibrillatory at concentrations that did not affect cardiac function: neither left ventricular developed pressure nor coronary perfusion pressure were affected. The effect of PDBu was antagonized by staurosporine: the incidence of VF was 17% in PDBu+staurosporine treated hearts (P < 0.05 vs control). To further study the profibrillatory effect of PDBu, hearts were exposed to PDBu in the presence of the ATP-dependent potassium channel antagonist glibenclamide. The latter prevented PDBu-induced VF. The results show that under the conditions employed, PDBu-induced activation of PKC induces redistribution of PKC activity and is associated with the development of VF.
J Mol Cell Cardiol 1993 Dec
PMID:Phorbol ester-induced ventricular fibrillation in the Langendorff-perfused rabbit heart: antagonism by staurosporine and glibenclamide. 815 62

It was recently reported that in rats exposure to heat shock leads to appearance of a myocardial heat shock protein (HSP 70) and to an increase in myocardial catalase activity. This correlated with an improvement in post-ischemic function either in Langendorff-perfused hearts after low-flow ischemia or in working hearts after short-term, no-flow ischemia. We investigated the effect of the same hyperthermic treatment on functional recovery from no-flow ischemia of various durations in isolated working rat hearts performing at high or low external workloads. Rats were heated to core temperature of 42 degrees C for 15 min. No significant protein oxidation (% oxidized methionine) was observed 2.5 hr after treatment. A protein with migration characteristics similar to HSP 70 was observed in hearts of heat shocked rats 24 hr after this treatment while their myocardial catalase activity was not increased. Hearts of similarly treated rats were excised 24 hr after hyperthermia and perfused in a working mode with Krebs-Henseleit buffer (1.25 mM Ca2+, 11 mM glucose). At 15 cm H2O preload and 100 cm H2O afterload after 30 min no-flow ischemia, control hearts recovered to 36.9%, 2%, 47.6%, and 21.5% of the preischemic values of heart rate-peak systolic pressure product (RPP), aortic output, coronary flow, and cardiac output, respectively. After only 25 min of ischemia the respective recovered values were 61.6%, 11.5%, 58.7%, and 33.5%. Throughout the recovery period these hemodynamic values were consistently higher in hearts of heat shocked animals than in those of control hearts but the differences were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1993 Dec 22
PMID:Role of catalase in myocardial protection against ischemia in heat shocked rats. 817 41

Myocardial fatty acid metabolism may be impaired in adriamycin cardiomyopathy. In order to determine the extent of fatty acid metabolism alterations, we measured steady state [14C]palmitate oxidation and the incorporation of [14C]palmitate into the neutral lipid pool in a rat model of adriamycin cardiomyopathy. Isolated hearts from control rats and rats treated with adriamycin were perfused with 1.2 mmol/l of [14C]palmitate for 30 min to achieve steady state oxidation measured as [14C]O2 production; then perfused with 1.2 nmol/l of unlabelled palmitate. Hearts were killed early (0-5 min) or late (10-30 min) after the [14C]palmitate perfusion, to determine incorporation into the neutral lipid pool, and neutral lipid utilization. In the control group steady state oxidation was reached in 10 min ([14C]O2 production = 580 +/- 61 nmol/min/g dry wt) of perfusion. In the adriamycin treated group, mean CO2 production was significantly reduced at 10 min (329 +/- 44 nmol/min/g dry wt, P < 0.01 v control). At 30 min, [14C]O2 production in the treated group was not significantly different than controls (521 +/- 65 nmol/min/g dry wt v 617 +/- 36 nmol/min/g dry wt, P = N.S.). The incorporation of [14C]palmitate into the neutral lipid pool measured in the early subgroup was significantly reduced for adriamycin treated hearts v controls (7.2 +/- 0.6 v 12.0 +/- 1.4 mumol/g dry wt respectively, P < 0.01). In the control group 14C labelled neutral lipid reduced with time to 8.4 +/- 1.1 mumol/g dry wt (P < 0.05) in the late group. The adriamycin group demonstrated no significant change between early and late measurements. In conclusion, in adriamycin cardiomyopathy: (1) there is significant delay in achieving steady state palmitate oxidation, although the steady state rate is near normal; (2) palmitate incorporation into the neutral lipid pool is reduced; (3) neutral lipid pool utilization may also be reduced. These data suggest impaired uptake of palmitate into the cell in adriamycin cardiomyopathy, with a relatively maintained capacity for oxidative metabolism.
J Mol Cell Cardiol 1994 Jan
PMID:Alterations in fatty acid metabolism in adriamycin cardiomyopathy. 819 63

Adenosine and acetylcholine exert negative chronotropic and anti-adrenergic effects on nonischemic myocardium presumably via receptor coupling to the same or similar inhibitory guanine nucleotide binding protein (Gi). To determine whether the cardioprotective effect of adenosine is mediated via adenosine A1 receptor coupling to Gi proteins, isolated rat hearts, perfused at constant pressure and constant heart rate, were subjected to 30 min global normothermic (37 degrees C) ischemia and 45 min reperfusion. Untreated control hearts recovered 52 +/- 2% of preischemic left ventricular developed pressure (LVDP). Hearts treated for 10 minutes prior to ischemia with adenosine (100 microM) and the adenosine A1 receptor agonist cyclohexyladenosine (CHA, 0.25 microM) recovered 67 +/- 4% and 70 +/- 4%, respectively. Hearts treated with the non-specific muscarinic cholinergic agonist carbamylcholine (1 microM) exhibited similar enhanced postischemic recovery (70 +/- 3%). Pretreatment of rats with pertussis toxin (25 micrograms/kg i.p., 48 h prior to isolation) significantly reduced the negative chronotropic effects of adenosine and CHA. Pertussis toxin pretreatment also blocked the beneficial effects of adenosine (57 +/- 4% recovery) and CHA (49 +/- 4% recovery) on postischemic function. These results support the hypothesis that the salutary effect of adenosine on the ischemic myocardium is mediated via adenosine A1 receptor coupling to a pertussis toxin sensitive G protein, presumably Gi.
J Mol Cell Cardiol 1993 Jul
PMID:Pertussis toxin blocks adenosine A1 receptor mediated protection of the ischemic rat heart. 823 Feb 43

A causative factor in the development of diabetes-induced heart dysfunction may be abnormalities in myocardial energy metabolism. Using 13C-NMR spectroscopy, we investigated the effects of experimentally induced diabetes (streptozotocin 65 mg/kg, i.v.) on glucose metabolism and contractile function in the isolated perfused rat heart. Hearts from streptozotocin-treated and untreated control rats were perfused with 11 mM [1-13C]glucose as substrate and 1H-decoupled 13C-spectra recorded for up to 90 min. Incorporation of label from [1-13C]glucose into lactate and glutamate was observed in hearts from control animals, consistent with metabolism through glycolysis and TCA cycle, respectively. Diabetic hearts did not incorporate label into lactate or glutamate. Addition of insulin (0.05 U/ml) to the buffer resulted in the appearance of [3-13C]lactate, although glutamate labeling was not observed. Addition of insulin plus dichloroacetate (2 mM) resulted in incorporation of label from [1-13C]glucose into 2-, 3- and 4-13C-glutamate, indicating glucose entry into the TCA cycle. Addition of insulin, or insulin plus dichloroacetate to control hearts did not alter labeling of either lactate or glutamate. Cardiac function in hearts from the diabetic group was depressed compared to controls and declined significantly over the duration of the experiment. These studies show that concomitant with a decrease in cardiac function, glucose oxidation is profoundly inhibited following the induction of diabetes with streptozotocin. These observations are consistent with a combination of decreased glucose transport and a decrease in pyruvate dehydrogenase activity.
J Mol Cell Cardiol 1993 Oct
PMID:A 13C-NMR study of glucose oxidation in the intact functioning rat heart following diabetes-induced cardiomyopathy. 826 54

The present study was undertaken to determine whether quinidine may improve ischemia/reperfusion-induced functional and metabolic injury of isolated rat hearts. Thirty-five-min ischemia and the subsequent 60-min reperfusion resulted in no post-ischemic force generation, an increase in left ventricular end-diastolic pressure (about 1500%) and a sustained rise in perfusion pressure (136 +/- 15% of initial). This was associated with an increase in the release of creatine kinase and ATP metabolites from the reperfused heart, a decrease in tissue high-energy phosphates, changes in tissue sodium, calcium, potassium and magnesium contents, and a reduction in the triphenyltetrazolium chloride (TTC)-stained area, an indicator of infarction. Hearts were treated with 3-100 microM quinidine 3 min before ischemia. Quinidine at concentrations of 10 microM or greater resulted in post-ischemic contractile recovery in a concentration-dependent manner (61 +/- 8 to 95 +/- 8% of initial). Ischemia/reperfusion-induced metabolic and histologic alterations were also suppressed by treatment with quinidine in a concentration-dependent manner. The results suggest that quinidine has a cardioprotective effect in ischemic/reperfused hearts. Because transmembrane fluxes of ions, substrates, and enzymes were suppressed by treatment with quinidine, protection of cardiac cell membrane function and/or integrity against ischemia/reperfusion-induced ionic imbalance, presumably sodium imbalance, across the sarcolemma is a possible mechanism by which quinidine may act. Slightly higher levels of ATP were detected in the treated hearts at 10 and 15 min, but not at 35 min of ischemia. Such preservation of high-energy phosphates might also be beneficial for protecting myocardial cells against ischemic damage.
J Mol Cell Cardiol 1993 Oct
PMID:Beneficial effects of quinidine on post-ischemic contractile failure of isolated rat hearts. 826 56

To test the hypothesis that stunning is due to a decreased sensitivity of the myofibrils for calcium, we compared the isometric force-Ca2+ relation in skinned trabeculae from stunned and control hearts. Hearts were made ischemic for 40 min followed by 30 min reperfusion. In one group (Group 1) changes in left ventricular systolic and diastolic pressure were monitored. From another group (Group 2), trabeculae were isolated to determine the relation between force and Ca2+ concentration. Trabeculae isolated from hearts (Group 3) perfused aerobically for 90 min served as controls. Left ventricular developed pressure and end diastolic pressure were 5.9 +/- 0.7 kPa and 5.8 +/- 0.7 kPa, respectively in stunned hearts as compared to 9.9 +/- 1.2 kPa and 1.2 +/- 0.1 kPa prior to ischemia. The nucleotide content decreased from 24.9 +/- 3.4 mumol.g-1(dw) in control hearts to 9.3 +/- 0.8 mumol.g-1(dw) after ischemia and reperfusion while the creatine kinase levels were about the same. Force-Ca2+ relations obtained from trabeculae from control and stunned hearts were fitted to the Hill equation. Maximal isometric force, the midpoint and the steepness of the curves estimated for the two groups were not significantly different. We conclude that the maximum isometric force and the sensitivity of the contractile apparatus of skinned myocardium of stunned hearts do not differ from that of control hearts. This suggests that structural changes of the contractile proteins leading to a decreased sensitivity of the myofibrils to calcium are not involved in the mechanism responsible for stunning.
J Mol Cell Cardiol 1993 May
PMID:Stunning does not change the relation between calcium and force in skinned rat trabeculae. 837 14

The relationship between myocardial triglyceride content and 1H NMR visible fatty acid resonance intensity was investigated. Hearts from rats fed a 20% rapeseed oil diet contained markedly increased levels of triglycerides as judged by thin layer chromatographic analysis. This elevation in cardiac triglycerides was associated with sharp increases in the cell volume occupied by lipid droplets and in 1H NMR visible fatty acid resonances. Spin-lattice and spin-spin relaxation times of the 1H NMR visible fatty acid resonances from myocardium of rapeseed oil-fed rats were similar in value to those measured for neat triolein. Additionally, the fatty acids constituting these enhanced 1H NMR visible resonances were metabolically active. Perfusion of triglyceride enriched hearts in the presence or absence of glucose caused a time-dependent decrease in the intensity of their 1H NMR visible fatty acid resonances. In contrast, perfusion with glucose+acetate essentially prevented this time-dependent decrease in 1H NMR visible fatty acid resonances. Morphometric analysis of these hearts demonstrated that the decrease in 1H NMR resonance intensity correlated with changes in the cell volume of triglyceride-enriched lipid droplets. These results demonstrate that metabolically active stores of cardiac fatty acids, presumably triglycerides, are 1H NMR visible. Further, they indicate the possible utility of 1H NMR spectroscopy in the future study of myocardial triglyceride metabolism.
J Mol Cell Cardiol 1993 May
PMID:Morphometric analysis demonstrates that metabolically active cardiac triglycerides are 1H NMR visible. 839 4


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