ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The androgenic steroid hormone testosterone induced an early (<30–60 seconds) stimulation of endocytosis, hexose transport, and amino acid transport, monitored by the temperature-sensitive uptake of horseradish peroxidase, 2-deoxyglucose, and α-aminoisobutyrate, respectively, in rat ventricle cubes and acutely isolated ventricular myocytes. This stimulation was time-and concentration-dependent and was maximal at 10-9to 10-8M testosterone, consistent with androgen-receptor mediation. EGTA (2.5 mM), La3+(1 mM), and verapamil (100 μM) ablated the hormonal response. The calcium ionophore A23187 (10 μM) induced an acute stimulation of endocytosis, amino add transport, and hexose transport which was not further increased by testosterone (10-8M), suggesting a common effector pathway. Testosterone (10-8M) also evoked a rapid (<30 seconds) stimulation of45Ca influx and efflux. Testosterone (10-8M) induced a rapid (<5 seconds) transient increase in ornithine decarboxylase (ODC) activity peaking (twofold to threefold) at 60 seconds, and an early (15 seconds) transient accumulation of polyamines peaking at 60 seconds In isolated myocytes. The specific, irreversible ODC inhibitor α-difluoromethylornithine (DFMO, 5-10 mM) blocked the testosterone-evoked increase in ODC activity and polyamine levels and the stimulation of Ca2+fluxes, endocytosis, hexose transport, and amino acid transport. Putrescine (0.5-1 mM), the ODC product, reversed DFMO inhibition and restored the increase in polyamines,45Ca fluxes, and Ca2+-dependent membrane transport processes. These results demonstrate that rapid, transient ODC-regulated polyamine synthesis is essential for androgenic stimulation of Ca2+fluxes and membrane transport processes in ventricular myocytes. These findings support a model for signal transduction in which newly synthesized polyamines serve as intracellular messengers to regulate transmembrane Ca2+movements, Ca2+-dependent membrane transport functions, and other Ca2+-and polyamine-sensitive processes in cardiac myocytes.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Tricuspid valve orifice and tricuspid valve anulus areas were measured simultaneously in the anesthetized dog with a newly developed area-measuring system based on electromagnetic induction. This system permitted real-time monitoring of the area enclosed by the edges of valve leaflets and by the juncture of the valve leaflet and the cardiac wall in situ, without artificial constraint to the valve motion. Right atrial and right ventricular pressures were measured with two catheter-tipped micromanometers. During control state, tricuspid valve orifice area (TOA) increased up to its peak [1.38±0.26 cm2(mean±SD)] coincidently with either atrial systole or rapid ventricular filling. Atrial contraction evoked distinct presystolic tricuspid anulus narrowing with concomitant slow TOA reduction. This slow TOA reduction began 30.0±16.1 msec before systolic atrioventricular pressure crossover, and the following rapid TOA decrease was completed 38.7 ±12.2 msec after systolic atrioventricular pressure crossover. TOA began to increase 48.4±30.4 msec before diastolic atrioventricular pressure crossover at the end portion of the isovolumic relaxation phase, opposing residual transvalvular pressure gradient (3.33±1.79 mm Hg). The slow presystolic TOA decrease was considered to be a reflection of the presystolic anulus narrowing caused by atrial systole. An Isolated atrial contraction induced by administering 1 mg acetylcholine chloride into the atrioventricular node artery or by vagus nerve stimulation could produce complete valve closure. Even in an isolated atrial contraction, the inflection point that marks the boundary between slow "atriogenic" closure presumably due to anulus narrowing and rapid closure presumably due to hemodynamic force was easily identified.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

To examine the effects of ischemic preconditioning on efferent autonomic responses following acute transmural myocardial ischemia/infarction (MI), the time course and extent of efferent sympathetic and vagal denervation were compared between control dogs that received a one-stage sustained coronary occlusion and preconditioned dogs that received four 5-minute coronary occlusions separated by 5 minutes of reperfusion before sustained occlusion. Effective refractory periods (ERP) basal and apical to MI were determined in the baseline state and during neural stimulation before and after preconditioning occlusions and 20, 60, 120, and 180 minutes after sustained occlusion by ligature ligation of diagonal branches of the left anterior descending coronary artery. In 10 control dogs with transmural MI, ERP shortening induced by bilateral ansae subclaviae stimulation (4-msec pulses, 2-4 Hz and 2-4 mA) was unchanged at basal sites but was attenuated at apical sites. Four of 40 apical test sites exhibited efferent sympathetic denervation (±2 msec shortening) 20 minutes after sustained occlusion. Thirteen of 40 apical sites became denervated during a 3-hour period. In 10 preconditioned dogs, ERP shortening at apical sites was unchanged after preconditioning occlusions and during the first 60 minutes of sustained ischemia but was attenuated at 120 minutes. Three of 40 apical test sites became denervated during a 3-hour period. The cumulative percentage of denervated apical test sites was significantly less in the preconditioned group compared with the control group (p=0.006) despite a comparable degree of subepicardial involvement in the MI (8.2±1.0percent; vs. 8.4±1.4percent;, the ratio to the left ventricular circumference, mean±SEM). In 11 control dogs tested for efferent vagal response after MI, ERP prolongation induced by bilateral vagal stimulation (4-msec pulses, 20 Hz with current strength 0.05 mA greater than that required to produce asystole) was unchanged at basal sites, but was attenuated at apical sites, and five of 44 test sites exhibited denervation (±1 msec prolongation) 20 minutes after sustained coronary occlusion. Fourteen of 40 apical sites became denervated during a 3-hour period. In 10 preconditioned dogs, vagally induced ERP prolongation was unchanged both at basal and apical sites, and none of 36 apical test sites exhibited denervation after preconditioning and during a 3-hour period of sustained coronary occlusion (p<0.001 vs. control group) despite a comparable degree of subendocardial involvement in the MI (11.8±0.8percent; vs. 11.9±1.3percent;). In preconditioned hearts, the blood flow reduction to the ischemic myocardium measured by radioactive microspheres during sustained coronary occlusion was comparable with that during the first preconditioning occlusion, indicating that an increase in collateral blood flow during MI cannot explain the protective effects of preconditioning. We conclude that preconditioning with brief episodes of ischemia preserves efferent sympathetic and vagal responses during the early period after coronary artery occlusion in the dog by mechanisms still to be determined.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

A model of one-dimensional action potential propagation was used to compare activation times and recovery times measured from simulated unipolar and bipolar electrograms with the activation and recovery times measured from simulated transmembrane action potentials. Theory predicts that the intrinsic deflection-the time of the maximum negative slope of the unipolar electrogram QRS complex-corresponds to the time of maximum positive slope of action potential depolarization. Similarly, the time of the maximum positive slope of the unipolar electrogram T wave corresponds to the time of maximum negative slope of action potential repolarization. This study showed that the difference between the unipolar electro- gram activation time and the action potential activation time and the difference between the unipolar electrogram recovery time and the action potential recovery time were small during ideal conditions of uniform propagation in a long cable. Nonideal conditions, however, were associated with activation time differences in excess of 1.8 msec and recovery time differences in excess of 30 msec (243 msec in certain conditions). Nonideal conditions that had a major influence were changes in activation sequence, propagation in a short cable, and propagation through regions of nonuniform coupling resistance and/or nonuniform membrane properties. Nonideal conditions that had a smaller influence were variations in distance from the measurement site to the simulated tissue surface, nonzero reference potentials, and the addition of distant events. Recovery time differences were more sensitive to the nonideal conditions than were activation time differences, and both depended on the action potential shape. When distant events significantly contributed to the unipolar electrogram waveform, the time differences when bipolar electrograms were used were less than those when unipolar electrograms were used; however, under other conditions, the time differences were comparable. Results showed that activation times and especially recovery times measured from electrograms can be greatly affected by conditions independent of changes in the underlying action potential waveforms.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The present study investigates the mechanism of endothelium-dependent relaxation of vascular smooth muscle. Melittin, a polypeptide found in honeybee venom and a known activator of phospholipase A2, induced transient, endothelium-dependent relaxations of rat thoracic aortae contracted with norepinephrine. Higher concentrations of melittin induced relaxations followed by contractions. Prior incubation of melittin with trypsin abolished the changes in relaxation and contraction due to melittin. Melittin (10 μg/ml)-induced relaxations were associated with transiently elevated levels of cyclic GMP with a peak increase of 30-fold, which occurred 30 seconds after melittin exposure. Melittin (10 μg/ml) elevated cyclic AMP levels less than twofold and this effect was variable. A lower concentration of melittin (1 μg/ml) elevated cyclic GMP levels approximately twofold, while exposure to 1 μg/ml melittin in the presence of the cyclic GMP phosphodiesterase inhibitor, M&B 22948 (1 mM), increased cyclic GMP levels fivefold. Removal of the endothelium prevented the increased levels of cyclic GMP and cyclic AMP due to melittin. Exposure to the guanylate cyclase inhibitor, methylene blue, prevented the increased levels of cyclic GMP. Methylene blue, nordihydroguaiaretic acid, and the phospholipase A2inhibitor, parabromophenacyl bromide, inhibited melittin-induced relaxations, while the cydo-oxygenase inhibitor, indomethacin, was without effect. Arachidonic acid increased cyclic AMP levels but had no effect on cyclic GMP levels in the presence or absence of indomethacin. Relaxations to melittin, and to the endothelium-dependent vasodilators acetylcholine, trypsin, histamine, and the Ca2+ionophore A23187, and/or the associated increased cyclic GMP levels, were reduced following exposure to melittin. Prior exposure to polyarginine (10 μg/ml), which induced endothelium-dependent relaxations that were prevented by methylene blue, also inhibited relaxations to the endothelium-dependent vasodilators. In contrast, relaxations to sodium nitro-prusside were potentiated in tissues previously exposed to melittin. Removal of the endothelium by rubbing the intimal surface also potentiated relaxations to sodium nitroprusside. Scanning electron micrographs of the intimal surface demonstrated that melittin and polyarginine greatly damaged the endothelial cells. The present results suggest that polycation containing peptides induce endothelium-dependent relaxation through elevation of cyclic GMP levels within the smooth muscle. Furthermore, these peptides may desensitize tissues to endothelium-dependent vasodilation by causing damage to the endotheUal cells.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Discontinuous density sucrose gradient centrifugation was used to isolate membrane vesicles from the left ventricle of three normal subjects (one prospective organ donor and two traffic victims whose hearts were obtained 1 hour after death) and nine patients undergoing cardiac transplantation as a consequence of idiopathic dilated cardiomyopathy. Sarcolemma-enriched subcellular fractions, detected in the interface between 8.55percent; and 25percent; sucrose, were identified by the increased activity of Na+, K+-ATPase and by enrichment in β-adrenergic receptor density. The density of β-adrenergic receptors was lower in vesicles from diseased hearts (610±71 fmol/mg protein) than in vesicles from normal hearts (1,410±226 fmol/mg protein; p<0.01). α1-Adrenergic receptors were identified in these membrane vesicles by [3H]prazosin binding. Specific binding of [3H]prazosin was about 50percent; of the total binding at 1 nM, and a,-adrenergic binding sites were saturable at approximately 3 nM. Scatchard analysis revealed 58±5 fmol/mg protein (KD= 0.90±0.08 nM) in pathological hearts and 30±5 fmol/mg protein (KD=0.90±0.03 nM) in normal hearts (p<0.01). The displacement curve of (-)-norepinephrine in membrane vesicles from normal hearts delineated one subpopulation of α1-adrenergic receptors; the addition of 0.1 mM GTP did not cause right shift. In membrane vesicles from diseased heart, the displacement curve of (-)-norepinephrine disclosed two subpopulations of α1-adrenergic receptors. A right shift that occurred after addition of GTP showed that in this case α1-adrenergic receptors were functionally coupled with GTP-binding protein. This study demonstrated the presence of α1-adrenergic receptors in sarcolemma-enriched subcellular fractions from both normal and idiopathic dilated cardiomyopathic hearts. Only α1-adrenergic receptors from pathological hearts were coupled to GTP-binding protein.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Atrial wall stretching is a known stimulus for atrial natriuretic peptide (ANP) secretion. The effects of the stimulation of autonomic nervous system, hemodynamic factors, and humoral factors (epinephrine, angiotensin, vasopressin, and brain extracts) on the release of ANP under basal conditions and during increased atrial pressure produced by acute volume loading in pithed rats were examined. In conscious rats, acute volume expansion by 0.9percent; of saline (4 ml) increased the plasma immunoreactive ANP (IR-ANP) concentrations by a factor of 4 (140±30 pg/ml vs. 521±140 pg/ml, p<0.001, n=8), whereas volume-induced ANP release was blocked in pithed rats (75±9 pg/ml vs. 99±13 pg/ml, NS, n=7). The ANP versus right atrial pressure curve shifted to the right, indicating that much smaller amounts of IR-ANP were released in pithed than in conscious rats for each given increase in right atrial pressure. Electrical vagal and sympathetic nerve stimulations or changes in heart rate had no effect on plasma IR-ANP concentrations and failed to restore the volume-load-induced release of ANP in pithed rats. When extracts of anterior pituitary lobe, brain cortex, or hypothalamus were infused, no effect on volume-expansion-induced plasma IR-ANP levels was seen. In contrast, acute volume expansion caused a fourfold increase in levels of circulating IR-ANP in pithed rats that received posterior pituitary extracts, and the ANP versus right atrial pressure curve shifted markedly to the left. Infusion of a V1antagonist blocked the volume-expansion-induced ANP release produced by the posterior pituitary extract. When [Arg8]-vasopressin (0.025 or 0.05 μg/kg/ min) was infused to pithed rats, mean arterial pressure increased but basal plasma IR-ANP did not change significantly. However, acute volume expansion in the presence of vasopressin infusion (0.05 μg/kg/min) increased the amount of circulating IR-ANP by a factor of 4 (113±14 pg/ml vs. 414±43 pg/ml, p<0.001, n=8). Thus, for a given increase in right atrial pressure, a similar amount of IR-ANP was released in the pithed rat during the vasopressin infusion as in the normal conscious animal. V1antagonist blocked the increase in mean arterial pressure as well as the increase of plasma IR-ANP produced by [Arg8]-vasopressin. In addition, volume expansion during intravenous epinephrine (1.75 μg/kg/min) and angiotensin (1.0 μg/kg/min) doubled plasma IR-ANP levels. These results indicate that pressor hormones, especially vasopressin, restore the ability of volume expansion to induce ANP release in the pithed rat. The combined effect of right atrial pressure and pressor hormones in regulating ANP release is a new mechanism by which humoral stimulation modulates the direct, mechanical-stimulus-induced hormone secretion.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Cardiac myocytes isolated from adult rat hearts were grown on laminin coated culture dishes for more than a month. During this time, the cells underwent a morphological transformation which has also been referred to by others as cell remodeling (Guo J-X, Jacobson SL, Brown DL: Cell Mot Cytoskeleton 1986; 6:291–304). This results in a change in myocyte morphology from its typical in vivo cylindrical shape to one which is more pleiomorphic. Despite the long-term change in morphology, myocytes expressed for differing lengths of time several aspects of the adult phenotype as evidenced by the following: 1) maintenance of cylindrical shape and/or evident cross-striations for the first 24–48 hours in culture, 2) reappearance of cross-striations during the second week in culture, 3) little or no spontaneous contractility for the first 4 days in culture, 4) expression of only the V1isoform of myosin for at least 7 days, and 5) altered myosin isoform expression in response to changes in environmental conditions. These factors taken together suggest that in culture the adult cardiac myocyte remains a highly differentiated cell (as opposed to possible dedifferentiation) and maintains many of its previous in vivo characteristics. Such highly differentiated adult cells should be suitable as an in vitro system for studying the direct cellular effects of factors which regulate growth and differentiation of the in vivo heart.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

By comparing in situ negative staining of mammalian heart muscle using La(NO3)3with conventional positive staining by uranium and lead salts, we showed that 1) the membrane area of rat cardiac gap junctions (GJs) at the intercalated disks is threefold to fourfold greater than previously thought; 2) connexon arrays of cardiac GJ are subdivided into microdomains by connexon-free aisles; 3) profiles of GJ-associated vesicles (GJAVs) of plasmalemmal origin (which are present extracellularly and sharply localized at three extracellular sites) are paired to form GJs with each other and with myocyte plasmalemma; 4) some GJAVs contain arrays of assembled connexons; and 5) myocytes contain intracytoplasmic complexes lying within cylindrical or cigar-shaped membranes and consisting of GJs and multiple vesicles apparently dissociating from these GJs.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID