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Biomedical subjects

H Heinle

Publications and source records attributed to H Heinle.

At least 37 records · Page 2Linked to original sources

Cigarette smoking, blood lipids, and baroreceptor-modulated nociception.

Activation of arterial blood pressure has been shown to influence higher central nervous activity. In animals, induction of sleep-like states and increases of seizure and pain thresholds in response to baroreceptor stimulation have been reported. In certain human groups, mechanical stimulation of the carotid baroreceptors also increases pain thresholds. The present paper examines the hypothesis that smokers show baroreceptor dependent antinociception as compared to non-smokers. It is speculated that one effect which rewards smoking is the nicotine induced phasic blood pressure increase which leads to baroreceptor stimulation and dampens pain perception. One hundred and twenty subjects were investigated using a recently developed mechanical baroreceptor stimulation technique and an electrical pain stimulus. The group of heavy smokers showed the predicted effect: their pain thresholds were enhanced during conditions of increased baroreceptor activity as compared to the control condition. The group of medium, light and non-smokers, however, did not show this effect. Neither blood lipid levels nor diastolic or systolic blood pressure paralleled the group differences on baroreceptor dependent antinociception. In heavy smokers, the nicotine induced phasic blood pressure increases might have baroreceptor dependent pain dampening effects, which might be among the reinforcing qualities of smoking.

Adult↗

The influence of oxidatively modified low density lipoprotein on parameters of energy metabolism and contractile function of arterial smooth muscle.

Recently published results provide evidence of the importance of oxidatively modified LDL in the development of atherosclerosis. Several typical characteristics of this disease can be ascribed to the effects of oxidized LDL on the different cells involved in lesion formation. In various cell culture systems oxidized LDL was found to be cytotoxic. Therefore we were interested in its influence on parameters of energy metabolism such as glycogen and ATP content as determined for aortic segments in vitro. The results show that oxidized LDL leads to sharp decreases in both parameters, indicating an activation of cellular energy metabolism. Findings obtained from contraction experiments in which oxidized LDL shows a concentration-enhancing effect on arterial segments suggest that the oxidized lipoprotein facilitates cellular Ca2+ liberation. This seems to be a common signal leading to its effects on energy metabolism and contraction and could also explain its cytotoxicity if cells are exposed to it for longer periods.

Adenosine Triphosphate↗

Calcium antagonists and atherosclerosis.

Numerous trials have used calcium antagonistic substances to inhibit or prevent genesis and progression of atherosclerosis, as well as disintegration of intimal proliferates and calcium deposition in atheromas or in matrix tissue of artery walls. In experimental models, various components involved in the development of atherosclerosis can be influenced by calcium antagonists. Transendothelial transport through interendothelial spaces and through the endothelial cells are sensitive to calcium antagonists of various types. Some drugs with calcium antagonistic properties are capable of inhibiting the development of stenosing proliferates caused by ballooning or other types of local artery wall stimulation. With cultures of cells obtained from normal and atherosclerotic arteries, insights into the mechanisms are possible by which various calcium antagonists influence the development and the progression of atherosclerosis.

Animals↗

Ca2+ influx in spontaneously hypertensive rats is sensitive to calcium antagonists.

Upon perfusion with a solution containing Ca2+, after Ca2+-free perfusion, aortic rings from spontaneously hypertensive rats (SHR) responded with a contraction. The contraction was usually transient. When verapamil or nifedipine were added prior to and during Ca2+ repletion, the force developed was reduced to 25% of that of uninhibited contraction. Aortas from normotensive rats did not show comparable properties. These findings demonstrate that calcium influx in aortic smooth muscle of SHR occurs mainly via voltage-dependent calcium channels.

Animals↗

Does the xanthine-xanthine oxidase system alter contractile behaviour of vascular smooth muscle?

Since xanthine oxidase (XOD) preparations are usually applied as crystalline suspensions in ammonium sulphate solution, we studied separately the contractile responses of excised rabbit carotid arteries to the free radical generating system of xanthine-XOD and ammonium ions. Using dialyzed XOD (0.1-0.2 U/ml) the contractile pattern of the xanthine-XOD system was characterized by initial contraction followed by relaxation. Identical contractile behaviour was observed when xanthine was omitted from that system. These contractile responses were indistinguishable from those obtained with ammonium sulphate (10-20 mM). The threshold concentration of ammonium sulphate for inducing contraction was 1-2 mM. Both Ca++-free solution and verapamil only slightly inhibited the contractions produced by XOD and ammonium sulphate. No contractile effect was observed with dialyzed XOD. We conclude that the contractile effects of the xanthine-XOD system on vascular smooth muscle are due to simultaneously applied ammonium ions, and our findings emphasize the need for further purification of XOD preparations when investigating their effects on smooth muscle.

Ammonia↗

Metabolite concentration gradients in the arterial wall of experimental atherosclerosis.

Development of intimal necrosis is characteristic of advanced atherosclerotic lesions. In order to study metabolic alterations preceding cellular death, the concentration gradients of glucose, glycogen, ATP, and lactate were measured within the walls of rabbit carotid arteries which were transmurally stimulated by dc impulses. This experimental model allows the induction of lipid-free intimal myocyte proliferations usually void of necrosis and, under additional hypercholesterolemia, typical lipid-laden atheromas, which become necrotic after 5-6 weeks of stimulation. Frozen samples (1 X 3 mm2) obtained from normal arterial wall and from both types of plaques as well as from spontaneously occurring aortic lesions of the hypercholesterolemic rabbits were cut in consecutive slices (10 microns thick) parallel to the luminal surface from the intima toward the adventitia. Compared with normal media, the results show that in the neointima the concentrations of glucose and glycogen decreased whereas that of lactate increased, independent of whether or not hypercholesterolemia was induced. The ATP concentration in lipid-free plaques was comparable with that in normal media, but strongly decreased in lesions which developed in combination with hypercholesterolemia. These observations support the view that in the initial stages of plaque growth, the intimal cells reveal an increased energy turnover leading to a decreased glycogen content. The development of necrosis, however, seems to involve additional events associated with a decrease in ATP, obviously depending on the effects of lipids or lipoproteins in the cells of the arterial wall.

Adenosine Triphosphate↗

Inhibition by verapamil of the medium change induced stimulation of cultured vascular smooth muscle cells.

Mitotic stimulation of vascular smooth muscle cells in confluent cultures as determined by increased thymidine incorporation is achieved by medium change, possibly by the action of serum derived factors. Results obtained by measuring 3H-thymidine incorporation, glucose uptake and lactate production of cultured smooth muscle cells show that application of verapamil, a calcium entry blocker, prevents the stimulating effect of medium change. It is concluded that this type of stimulation is triggered by an influx of calcium ions accessible to calcium antagonistic drugs. It seems possible that the antiatherosclerotic effect of verapamil is based at least to some extent on a similar mechanism.

Animals↗

Vasoconstriction of carotid artery induced by hydroperoxides.

The influence of hydroperoxides (hydrogen peroxide, t-butylhydroperoxide) on tone of arterial smooth muscle was studied. The results of the experiments which were performed with segments of rabbit carotid arteries under isometric conditions show that peroxide concentrations higher than 10(-4) M induced vasoconstriction. These contractions were reversible when glucose was present in the superfused solution. In the absence of glucose a long-lasting increase in tone was found. The contraction response persisted even in Ca2+-free solution. These results indicate a stimulatory effect of hydroperoxides on vascular smooth muscle probably related to a liberation of intracellularly bound calcium ions.

Animals↗

The binding of Evans blue to collagen and elastin in elastic tissue.

The binding of Evans blue to collagen and elastin in rabbit aortic tissue and in bovine ligamentum nuchae was studied following circulation in vivo of the dye and incubation in vitro in Evans blue containing plasma, respectively. Using collagenase and elastase, the dye was liberated from both tissues corresponding to their different contents of collagen and elastin. Disc electrophoretic analysis of the liberated dye showed, that it migrated as free Evans blue indicating that the binding of the dye to the macromolecules was due to spatial interactions rather than to fixation at specific prosthetic groups. The capability of collagen and elastin to bind Evans blue was demonstrated with the isolated proteins; it was shown elastin had a higher affinity to the dye than collagen. Treatment of the blued tissue with hyaluronidase and Triton X-100 showed that binding to complex carbohydrates and dye accumulation in the aqueous intra- or extracellular space seems to be negligible.

Animals↗

Binding properties of circulating Evans blue in rabbits as determined by disc electrophoresis.

Following injections of Evans blue (1-200 mg/kg) into rabbits, polyacrylamide gel disc electrophoresis showed that Evans blue binds to two protein fractions. The greater part was bound to albumin and the remainder to a plasma protein in the postalbumin fraction. Unbound Evans blue was present in each plasma sample analyzed. Attempts to liberate the dye from the coloured areas of the aorta and common carotid arteries by tissue electrophoresis failed unless very high concentrations of Evans blue were used. This indicates that at the concentrations used by many investigators areas dyed by Evans blue may not be equated with the presence of diffusible protein-dye complexes.

Animals↗

Oxygen and glucose withdrawal on portal veins: NADH fluorescence and spontaneous activity.

Parallel with the spontaneous mechanical activity, changes in steady-state levels of reduced pyridine nucleotides (PN) of rat portal veins were recorded by continuous monitoring of surface fluorescence. These data were correlated with changes in tissue concentrations of glucose, lactate and ATP when subjected to long-term anoxia and/or glucose depletion. In response to anoxia and addition of glucose the fluorescence intensity excited at 366 nm increased, representing a reduction of PN. This was accompanied by a higher tissue lactate content. Spontaneous contraction force decreased independently of accelerated glycolysis, which did not compensate for eliminated oxidative metabolism. The frequency of spontaneous contractions changed time-dependent. When O2 was added after more than 3 h of anoxia the spontaneous activity was restituted and PN were re-oxidized. Contraction relaxation cycles of spontaneous activity were accompanied by phasic changes of PN fluorescence clearly detectable in vessels supplied with glucose only. Suppressive effects of O2 and/or glucose depletion upon spontaneous contractile activity seem to be mediated more by alterations of cell membrane properties than by changes in energy metabolism.

Adenosine Triphosphate↗

Enhanced oxygen uptake and lactate production of smooth muscle cell proliferates of rabbit carotid arteries.

In rabbit carotid arteries intimal smooth muscle cell proliferations were induced by repeated local electrical stimulation of the artery wall. Oxygen uptake and lactate production of the proliferating tissue were determined in vitro and compared with the results obtained from nonstimulated arterial wall segments. Under the incubation conditions employed, oxygen consumption and lactate production of the proliferating tissue were 91.3 and 62.5 nmol x min-1 x mg-1 DNA, compared with the control values of 70.8 and 41.6 nmol x min-1 x mg-1 DNA. The DNA content of the proliferates and normal arterial wall tissue amounted to 9.6 and 12.0 microgram DNA x mg-1 dry weight. The results show that in proliferates obtained with the described procedure there is an increased capacity for ATP regenerating systems, respiration and glycolysis, indicating a modified function of the proliferating smooth muscle cells.

Animals↗

Biochemical variations in electrically induced intimal smooth muscle cell proliferates of the rabbit carotid artery.

Common carotid arteries of rabbits were locally stimulated every day by chronically repeated electrical impulses for periods up to 4 weeks. Morphological observations revealed that, primarily at the anodal site of the stimulated segment, smooth muscle cells penetrated from the media through the internal elastic membrane and proliferated in the subendothelial space below a morphologically unchanged endothelium. When the plasma cholesterol was raised by cholesterol feeding, typical atheromatous plaques were formed. Biochemical studies showed an increased metabolic activity of the proliferating cells; in comparison with normal intima-media, the tissue content of DNA, protein, and lactate was increased, whereas that of glucose and glycogen was decreased in the proliferates. Furthermore, during in vitro incubation, the uptake of oxygen and glucose and the production of lactate was enhanced. The increased energy consumption of the proliferates indicates a modified metabolic function of these cells.

Animals↗