摘要:

To determine whether oxygen metabolites can cause ductus relaxation, we used rings of fetal ductus obtained from 36 near-term lambs and measured the effects of the oxygen metabolites generated by the combination of hypoxanthine and xanthine oxidase. The oxygen metabolites produced by hypoxanthine plus xanthine oxidase caused relaxation of the ductus that was inhibited by catalase (hydrogen peroxide scavenger) but not by superoxide dismutase (superoxide anion scavenger). In addition, hypoxanthine plus xanthine oxidase produced a 14-fold increase in prostaglandin (PG) E2production with only twofold increase in 6-keto-PGFla(the stable metabolite of PGI2). PGE2is the most potent relaxant of the ductus arteriosus. The presence of either catalase or indomethacin blocked both the increase in prostaglandin production and the relaxation. We conclude that reactive oxygen metabolites relax the ductus arteriosus and oppose the normal constriction that occurs after birth. However, the vasoactive effects of reactive oxygen metabolites in the ductus appear to be mediated exclusively through the generation of PGE2.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Coronary vascular responses in regions of reversible postischemic myocardial contractile dysfunction (stunned myocardium) were examined in chronically instrumented, awake dogs. Left anterior descending coronary artery blood flow and oxygen extraction, aortic and left ventricular pressures, and regional myocardial segment shortening were determined. Regional myocardial blood flow was measured with microspheres. Coronary reactive hyperemia and vasodilator reserve, and regional myocardial oxygen consumption were determined. Three sequential 10-minute left anterior descending coronary artery occlusions separated by 30-minute reperfusion periods resulted in progressive postischemic dysfunction so that 1 hour after the final coronary artery occlusion, myocardial segment shortening was reduced to 37% of baseline. Despite this decrease in contractile function, left anterior descending artery flow (19.6±2.6 vs. 18.4±3.0 ml/min), myocardial blood flow and the transmural distribution of flow measured with microspheres, and regional myocardial oxygen consumption were unchanged. Although the coronary vasodilator reserve hi response to adenosine was unaltered (63±9 vs. 70±15 ml/min), the reactive hyperemia response to a 10-second coronary occlusion was decreased in intensity (debt repayment ratio=474±78% vs. 322±74%; p<0.05) and duration (57±9.1 vs. 35±4.5 seconds; p<0.05), while the peak flow response was unchanged (57±6.8 vs. 60±7.1 ml/min). Thus, in the intact awake animal postischemic myocardial contractile dysfunction was not associated with decreased myocardial oxygen consumption and did not impair the normal relation between coronary blood flow and myocardial oxygen utilization. Although coronary vessels showed a normal ability to vasodilate in response to adenosine, coronary reactive hyperemia was reduced.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The available data on F-actin microfilament distribution in vascular endothelial cells in vivo is limited. In this study, the appearance and distribution of endothelial cell microfilaments in the rabbit thoracic aorta, the abdominal aorta and its major arterial branch points, and the aortic bifurcation were examined. Perfusion fixed rabbit aortas were stained in situ for F-actin by infusing rkodamine phalloidin via a peristaltic pump into the aortas at a slow flow rate. This new technique resulted in excellent visualization of branch points and allowed for a precise description of the actin microfilament bundles in endothelial cells along flow dividers. In the thorack and abdominal aorta, away from branch ostia, actin microfilaments were localized in two regions of the endothelial cells, as a prominent band that completely outlined the cell periphery, and also as short central stress fibers. The central stress fibers were more frequent and prominent in cells of the abdominal aorta. At branch sites and at the aortic bifurcation, long, thick microfilament bundles were present in endothelial cells extending from the tip of the flow divider to a few millimeters along the branch arteries, the aorta, and the iliac arteries. Peripheral actin, however, no longer completely surrounded the cells. The thick bundles were not prominent in endothelial cells located adjacent to the proximal Up of branches or at the iliac arteries opposite the flow divider. This study shows that endothelial cell F-actin microfilament distribution in vivo is well defined along the aortic-arterial system. The prominent central microfilament bundles and the reduced peripheral microfilaments seen at localized regions may reflect an adaptive response to elevated shear stress at these sites.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

In an effort to determine whether arterial conductance vessels dilate in response to increased blood flow stimuli, brachial artery area (cm2) and diameter (cm) were derived by simultaneous measurement of forearm blood flow (ml/min-100 ml) and brachial artery blood flow velocity (cm/sec) following the release of arterial occlusion. Measurements were made at rest and at the time of maximal flow after the release of graded periods of forearm arterial occlusion (20 seconds to 10 minutes). These studies showed a graded large vessel dilation following occlusions of up to 1 minute (baseline diameter, 0.33±0.01; after 1 minute occlusion, 0.45±0.02 cm; P<0.05) after which time diameter plateaued (after 10 minutes of occlusion, 0.48±0.02 cm). In addition, the tune course of diameter and flow changes after 3 minutes of arterial occlusion were examined. Flow was maximal at 5 seconds but diameter was maximal at 15-30 seconds after release. Furthermore, the half time for the return of diameter to baseline was longer than that for blood flow. We also measured the diameter after forearm heating (42°C) and noted a substantial increase in diameter (before heating, 0.32±0.01; after heating, 0.39±0.02 cm; p<0.05). Finally, we applied pressure to the venous side of arteriovenous fistnlae in five hemodialysis patients. This maneuver was associated with large reductions hi forearm blood flow (baseline flow, 63.3±10.6; venous compression flow, 36.0±4.4 ml/min 100 ml;p<0.05) and a decrease in brachial artery size (baseline diameter, 0.63±0.07; venous compression diameter, 0.58±0.06 cm; p<0.05). We conclude that 1) the human brachial artery size changes in response to changes in blood flow, and 2) the maximal dilation occurs after maximal flow is noted. Although alternate explanations are possible for each of our observations, our results are most consistent with a flow-mediated, localized vasodilating process.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Previous studies indicate impairment of coronary arterial ring relaxation in response to acetykholine (ACh) following coronary reperfusion, mediated via loss of endothetium-derived relaxing factor (EDRF). To examine if coronary vasodilator reserve is reduced following coronary ocdusfon-reperfusion in intact animnk, 16 open-chest mongrel dogs were subjected to 1 hour of total left circumflex (Cx) coronary artery occlusion followed by reperfusion for 1 hour. Prior to Cx occlusion, coronary blood flow increased and vascular resistance decreased (both p±O.Ol) in response to ACh and bradykinin (BK). Following reperfusion, Increase in Cx coronary flow in response to both vasodilators was significantly (p±O.Ol) impaired. Myocardial histology showed extensive neutrophil infiltration and capillary plugging by neutrophils in the Cx compared with the left anterior descending coronary artery-supplied myocardium. Myocardial myetoperoxidase activity was also increased in the Cx compared with the left anterior descending region (p±0.02). Pretreatment of four dogs with indomethadn partially reduced the vasodilator response to BK but not to ACh. However, indomethadn did not affect reperfusion-induced attenuation of BK or ACh's coronary vasodilator effects. To determine if calcium blocker verapamil would modify reperfusion-induced impairment in coronary vasodilator reserve, six dogs were treated with verapamil. Although verapamil enhanced coronary vasodilator effects of ACh and BK, it did not modify reperfusion-induced attenuation of coronary vasodilator reserve. Myocardial neutrophil accumulation and myeloperoxidase activity was also similar in control, indomethacin, and verapamil-treated dogs. These observations suggest that coronary reperfusion impairs coronary vasodilator reserve in intact dogs. This impairment is not modified by prostaglandin inhibition or by calcium blockade. Besides loss of EDRF, capillary plugging by neutrophils may contribute to the altered coronary flow reserve observed in the immediate post-reperfusfon period. Furthermore, indomethacin or verapamil are not effective in modifying the reperfusion-related impairment of coronary vasodilator reserve.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Central catecholaminergic neurons are involved in cardiovascular regulation. Neuropeptide Y (NPY) coexists with adrenaline and noradrenaline in the rat brain, and interactions among these substances have been studied. The purpose of this study was to investigate the possible role of NPY in central cardiovascular control. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure was monitored intra-arterially. Intramedullary microinjection (60 nl) of NPY (0, 46.5 fmol, 465 fmol, 1.5 pmol, and 4.65 pmol) was made into the nucleus tractus solitarii (NTS), into the area postrema, and into the C1 area in the rostroventrolateral medulla. Injection site was identified by L-glutamate administration and confirmed histologically. Unilateral injection of NPY into the NTS produced a prominent dose-related decrease in heart rate and systolic and diastolic blood pressure (-106±8 beats/min, -56±2 mm Hg, and -33±2 mm Hg, respectively after 4.65 pmol NPY, n=7, p<0.001). Maximal changes occurred at 30 seconds and recovered in 10 minutes for blood pressure and 20 minutes for heart rate. Injection into the area postrema produced an initial increase in heart rate and mean blood pressure (+23 ±2 beats/min and +18 ±2 mm Hg) followed by a prolonged decrease in heart rate and mean blood pressure (-14±4 beats/min and -15±2 nun Hg, respectively, n=7, /?<0.01). However, injection of NPY into the Cl area produced a dose-related increase in blood pressure and a decrease in heart rate (+17±1 nun Hg and -23±8 beats/min, n=6, p<0.01). To test the specific effect of NPY, rabbit anti-NPY antiserum was used. Prior administration of the antiserum inhibited the effects of subsequent administration of NPY, whereas inactivated antiserum was not able to prevent these effects. These studies demonstrate that NPY has powerful cardiovascular effects in the NTS, area postrema, and Cl area of the medulla oblongata of the rat. This finding suggests that NPY may be important in cardiovascular regulation.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We examined the mechanism of the neutrophil (PMN)-dependent increase in pulmonary vascular permeability to protein after thrombin-induced pulmonary microembolism. Humoral factors that activate PMNs after thrombin-induced pulmonary microemboUsm were characterized in pulmonary lymph obtained from unanesthetized sheep challenged with intravenous infusion of α-thrombin. Tune-dependent increases in PMN migration, aggregation, and superoxide anion (O2-) generation were induced by the puhnonary lymph obtained within 20 minutes after thrombin infusion. The puhnonary lymph neutrophil activating factors present in ether extracts of lymph had retention times of leukotriene B4(LTB4) and monohydroxyeicosatetraenoic acids (HETEs) by high-performance liquid chromatography. The postthrombin lymph samples containing the LTB4and HETEs increased PMN O2-generation and endothelial monolayer permeability to125I-albumin in the presence of PMNs layered on the endothelial monolayers. Control lymph samples replete with LTB4, 5-HETE, and 15-HETE induced increases in PMN O2-generation and endothelial monolayer permeability toI25I-albumin in the presence of PMNs layered on the endothelial monolayers. Maximal increases in PMN O2-production and endothelial permeability occurred when LTB4, 5-HETE, and 15-HETE were coincubated with PMNs, indicating a synergistic action of these mediators in inducing PMN activation. Endothelial monolayer permeability to125I-albumin did not increase with postthrombin lymph samples obtained after pretreatment with the 5-lipoxygenase inhibitor, L-651, 392. The results indicate that lipoxygenase products generated in the lungs after thrombin-induced microembolism contribute to increased endothelial permeability secondary to PMN activation.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Exposure of adult mammalian myocardium to increased hemodynamic loads augments cardiac protein synthesis, ultimately leading to hypertrophy of the affected chamber. This established relationship between loading conditions and protein synthesis was examined in terms of two questions. First, is there a basic difference between the anabolic effect of a passive load imposed on diastolic myocardium and that of an active load generated by systolic myocardium? This issue was addressed by measuring [3H]phenylalanine incorporation into muscle protein in either quiescent or contracting ferret papillary muscles, set at known isometric lengths. Myocardial protein synthesis increased in proportion to total muscle tension in each case, with an equivalent relation describing both quiescent and contracting muscles. Synthesis of two contractile proteins, actin and myosin heavy chain, were enhanced by muscle loading. Thus, a quantitative rather than qualitative difference between the anabolic effects of diastolic and systolic loading was demonstrated. Second, since increased sodium influx is an initial cellular response requisite to the growth-inducing activity of many substances, and since sodium entry through stretch-activated ion channels is stimulated by deformation of the sarcolemma, does cardiac deformation during increased loading promote sodium influx as a signal to increase anabolic activity? In either quiescent or contracting papillary muscles, the rate of24Na+uptake was found to increase with load. Streptomycin, a cationic blocker of the mechanotransducer ion channels, was without effect on protein synthesis in stimulated but slack muscles; however, it inhibited, in a dose-related manner, the augmented protein synthesis otherwise observed in contracting muscles developing tension. At 500 μM, streptomycin did not reduce active tension, but it did reduce the synthesis of both actin and myosin heavy chain. In a second pharmacologic approach, inotropic agents were chosen which uniformly increased muscle tension development but which had contrasting effects on sodium influx. Protein synthesis increased in the presence of Na+influx enhancers, monensin or veratridine; however, protein synthesis decreased in the presence of amiloride, a sodium influx inhibitor. Thus, myocardial protein synthesis varied directly with sodium influx despite the positive inotropic effect observed with each of these agents. In addition, inhibition of protein synthesis by ouabain demonstrated that activation of the Na+pump is required for the anabolic effect of load. This study, therefore, identifies deformation-dependent sodium influx as an early signal in the transduction of load into growth in adult mammalian myocardium.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Do oxygen-derived free radicals, generated at the time of reperfusion, lethally injure viable, previously ischemic myocardium, damage vascular endothelium, and impair recovery of postischemic contractile function? To address these issues, 23 anesthetized open-chest dogs underwent 2 hours of left anterior descending coronary artery occlusion followed by 4 hours of reperfusion. Immediately prior to reflow, each dog was randomized to receive either the free radical scavenging agents superoxide dismutase (SOD)+catalase, or saline alone. SOD+catalase had no significant beneficial effect on infarct size measured by triphenyltetrazolium staining: area of necrosis averaged 38.5±6.1% vs. 46.3±6.2% of the area at risk in treated compared with control animals respectively (p=NS). Furthermore, infusion of SOD+catalase did not alter contractile function of the viable subepicardium: mean segment shortening (measured using sonomicrometry) at 4 hours postreperfusion was -23±5% of baseline, preocclusion values in controls dogs and -24±9% of preocclusion values in animals that received the scavenging agents. However, SOD+catalase treatment preserved the endocardial microvasculature (assessed by semiquantitative electron microscopic analysis) and enhanced regional myocardial blood flow after reperfusion. Specifically, mean score for microvascular injury was 0.41±0.14 vs. 0.10±0.08 (p<0.05) in control compared with SOD+catalase treated groups, and blood flow averaged 0.56±0.11 vs. 1.27±0.33 ml/min/g tissue (p<0.05), respectively, in the previously ischemic endocardium at 2 hours postreflow. Thus, SOD+catalase given at the time of reperfusion had no acute beneficial effect on either the extent of myocyte necrosis or postischemic contractile function in this canine model. SOD+catalase did, however, attenuate both endocardia! vascular injury and the "low reflow" phenomenon. These data suggest that microvascular injury and low reflow following prolonged (2 hour) but transient coronary occlusion may be mediated by oxygen-derived free radicals generated at the time of reperfusion.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Although it is recognized that the number of cardiac β-adrenoceptors is reduced in human dilated cardiomyopathy, the mechanisms involved have not been defined. We examined the possible role of altered humoral immunity by comparing the effect of sera from patients with idiopathic dilated cardiomyopathy (n=20), ischemic or valvular heart disease (n=28), or controls with no known cardiac disease (n=18) on the binding of radioligands to cardiac β-receptors. The ability of sera from cardiomyopathic patients to inhibit the binding of [3H]dihydroalprenolol to rat cardiac membranes was significantly higher than that of the other two patient groups (40±5% at 50-fold serum dilution compared to 14±3% for the ischemic/valvular heart disease group, and 14±4% for the normal control group, p<0.001). A similar inhibition was exerted by IgG from cardiomyopathic patients. Only the number, not the affinity, of the β-receptors was decreased by cardiomyopathic sera. This decrease could be prevented by preincubating the sera with anti-human IgG, indicating the presence of autoantibodies. Furthermore, the sera were ineffective against cardiac α1-adrenoceptors and considerably less effective against lung β2-receptors. In addition to ligand binding inhibition, sera from cardiomyopathic patients could immunoprecipitate β-adrenoceptors quantitatively from solubilized cardiac membranes. Positive sera inhibited significantly isoproterenol-stimulated adenylate cyclase with no effect on basal or NaF-stimulated activities. These results document the presence in sera from patients with idiopathic dilated cardiomyopathy of autoantibodies directed against the cardiac β-adrenoceptor which may play an important role in the regulation of inotropic responsiveness to β-agonists.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID