Biomedical subjects
O Lundgren
Publications and source records attributed to O Lundgren.
[The enteric nervous system. Untested field for specific pharmacotherapy].
Explore the source record for details and available documents.
Substance P effects on blood flow, fluid transport and vasoactive intestinal polypeptide release in the feline small intestine.
1. Substance P (SP) infusions were given close I.A. to the feline small intestine in vivo in a dose that produced plasma concentrations of 1-5 microM. This infusion regularly evoked a net fluid secretion measured with a gravimetric technique. Concomitantly, the release into blood of vasoactive intestinal polypeptide (VIP), a putative neurotransmitter of the enteric nervous system, increased. 2. The SP-induced fluid secretion was blocked by tetrodotoxin (7 micrograms close I.A.), a blocker of fast sodium channels in excitable tissues, and hexamethonium (10 mg (kg body wt)-1, I.V.), a nicotinic receptor antagonist, suggesting that the SP effect was mediated by the enteric nervous system. In line with this it was shown that the SP-evoked release of VIP was also significantly diminished by hexamethonium. 3. Close I.A. infusions of methionine enkephalin (Met-enkephalin; 7-23 nmol min-1) or electrical stimulation of the sympathetic nerve fibres (6 Hz) to the intestine markedly diminished net fluid secretion and the release of VIP caused by SP given close I.A. 4. The cyclo-oxygenase inhibitor diclofenac (5 mg (kg body wt)-1, I.V.) or the histamine-1 receptor antagonist pyrilamine (10 mg (kg body wt)-1, I.V.) did not influence the fluid secretion caused by SP, indicating that the effects of SP were not due to the actions of prostaglandins or histamine. 5. It is proposed that SP activates a nervous reflex arch that we have shown to be activated by various luminal stimuli, including cholera toxin.(ABSTRACT TRUNCATED AT 250 WORDS)
[The Nobel Prize in medicine].
Explore the source record for details and available documents.
Renal sodium excretion after oral or intravenous sodium loading in sodium-deprived normotensive and spontaneously hypertensive rats.
Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats that had been on a low sodium diet for 3 days were given 1.5 mmol sodium chloride kg-1 body weight either orally or intravenously. The rats receiving an oral sodium load showed a greater natriuresis than those receiving the same saline load intravenously. No increase of renal sodium excretion was observed when the rats received a hypertonic mannitol solution orally. The cumulative sodium excretion during the 8 h following oral loading was two to three times larger in SHR than in WKY, whereas no difference between strains could be demonstrated after giving saline intravenously. Furthermore, after switching from normal to low sodium diet the rate of decrease of renal sodium excretion was greater in SHR than in WKY rats. It is proposed that there exists a gastrointestinal sensory mechanism for sodium controlling the renal sodium excretion. Furthermore, it is suggested that the function of this mechanism differs between SHR and WKY.
The intestinal tract and the pathophysiology of arterial hypertension: an experimental study on Dahl rats.
Salt depleted rabbits and humans excrete an oral sodium load more quickly via the kidneys than an intravenous one. This has been ascribed to the presence of a sodium sensor in the gastrointestinal tract which in some way can influence renal function. The purpose of this study was to investigate this response in the Dahl rats. Renal and faecal sodium excretion was followed in the two strains of rats (normotensive, saltresistant (SR/Jr) and hypertensive, saltsensitive (SS/Jr) rats). After 4 days on a low salt diet they were given NaCl (1.5 mmol k(-1) body wt) either by gavage or intravenously. SR/Jr rats showed an increased renal sodium excretion both after oral and intravenous sodium repletion. The excretion was 2-3 times greater after th oral than after the intravenous administration. The SS/Jr rats augmented their renal sodium excretion only after the oral load, although the sodium excretion was significantly less than in SR/Jr rats. In fact, during the first 8 h after giving sodium orally the renal excretion of sodium was on an average eight times larger in the SR/Jr than in the SS/Jr rats. Renal excretion of sodium was similar in the two strains after intravenous administration. We conclude that the hypertensive SS/Jr rats have great difficulties in excreting an oral sodium load, a phenomenon that may be of importance in the pathophysiology of arterial hypertension in this strain of rats.
The small intestine, salt intake and arterial hypertension.
The possibility that the small intestine is of importance for the development of arterial hypertension is discussed in relation to the presence of an intestinal sodium sensor and an intestinal natriuretic factor. We propose that an intestinal sodium sensor upon activation releases a factor that evokes renal excretion of sodium. Based on observations made in the Dahl strain of hypertensive rats it is suggested that an attenuation of this mechanism may contribute to the development of arterial hypertension.
Partial purification of a factor from the feline small intestine causing natriuresis in vivo and inhibiting rubidium uptake into renal cells in vitro.
Small intestine of cat was homogenized under denaturing condition (6.0 M guanidinium chloride) in the presence of protease inhibitors and molecules in the 500 to 10,000 Da mass range were obtained by sequential ultrafiltrations. This material was separated by gel chromatography (Sephadex G-25), where fractions eluted in the mass range of 500-1000 Da inhibited 86Rb uptake into kidney slices in vitro. Furthermore, the same fractions exhibited a natriuretic effect when given intravenously to anesthetized rats. The gel chromatography fractions were further purified by cation exchange chromatography (CM-Sephadex C-25). Fractions eluted with a NaCl solution of around 250 mM inhibited 86Rb uptake into renal cortical tissue in vitro and showed natriuretic activity when tested in vivo in rats. It is proposed that intestine contains a water soluble natriuretic factor with an apparent molecular mass of 500-1000 Da. This material evokes a natriuresis in vivo and inhibits 86Rb uptake in vitro.
Free radicals and pathogenesis during ischemia and reperfusion of the cat small intestine.
BACKGROUND/AIM: In spite of the interest in free radicals as mediators of ischemic damage, most information on these species in biological systems is derived from indirect measurements. Our aim was to obtain more direct information concerning sources of free radical production during ischemia and reperfusion. METHODS: We have performed simultaneous measurement of radical generation, purine metabolites, reduced glutathione, neutrophil infiltration and morphological appearance in the cat small intestine in vivo during 60 minutes of ischemia followed by 60 minutes of reperfusion. RESULTS: Radical formation increased abruptly on reperfusion and remained elevated in untreated animals. Inhibition by a monoclonal antibody (IB4) against the neutrophil and by allopurinol treatment was paralleled by improvement of biochemical and morphological parameters. The radicals detected during reperfusion could be divided into one component arising directly from the neutrophils, one due to the xanthine oxidase reaction, and one unknown source. CONCLUSIONS: Neutrophils are a major source of radical production during reperfusion after ischemia. Radicals formed in the xanthine oxidase reaction seem to function as a primer for the neutrophils. The nonsignificant linear correlation between radical formation and morphological appearance suggests that factors other than free radicals are important for the development of intestinal damage after a period of ischemia.
Quantification of tissue damage in the feline small intestine during ischaemia-reperfusion: the importance of free radicals.
Intestinal ischaemia is accompanied by characteristic mucosal lesions, which can be graded according to a six-grade system proposed by Chiu et al. (1970). This report describes a continuous grading system which makes it possible to quantify the intestinal damage in connection with ischaemia-reperfusion. The present morphometric method is based on quantitative histological analysis of intestinal biopsies performed on 200 histological sections from 44 cat experiments. Radical formation was quantified by infusing close i.a. a spin trap, OXANOH, which produces a secondary stable radical, OXANO., after reacting with radicals in the tissue. OXANO. concentration was determined in venous blood samples with electron spin resonance. We demonstrate a highly significant correlation between the grading system of Chiu et al. (1970) and the morphometric analysis of this study. The tissue damage was located exclusively in the intestinal villi. Comparing the mucosal damage that occurs during 60 min of intestinal ischaemia (superior mesenteric artery pressure 15-25 mmHg) with that seen during the first 30 min reperfusion this study shows that the villus damage occurring during ischaemia is at least twice as large as the aggravation seen upon reperfusion. Furthermore, the authors demonstrate a significant correlation between rate of radical formation and villus tissue damage particularly during the first 30 min after ischaemia. It is concluded that the proposed quantitative morphological method represents a non-discrete grading system for evaluating tissue damage in connection with ischaemia-reperfusion in the small intestine. The ischaemia itself inflicted a more severe damage to the intestine than reperfusion. A significant correlation between damage and radical formation was demonstrated during the reperfusion. However, the results suggest that factors other than radical formation are of importance in explaining the tissue damage upon reperfusion. The nature of these factors is presently unknown.
Involvement of the myenteric plexus in the cholera toxin-induced net fluid secretion in the rat small intestine.
BACKGROUND: The enteric nervous system is responsible in vivo for most of the change in fluid transport induced by cholera toxin. The aim of the present study was to investigate the importance of the myenteric plexus in the Intramural reflex responsible for this secretion. METHODS: Long-term ablation of the myenteric plexus was achieved by serosal application of benzalkonium chloride on jejunal segments in rats. RESULTS: The treated segments without functioning myenteric plexus showed a normal net fluid absorption. Cholera toxin in this segment only induced a reduction of fluid absorption, whereas in a nontreated ileal segment it concomitantly induced a conspicuous net fluid secretion. Intravenous hexamethonium did not change the cholera toxin response in the treated jejunal segments, whereas vasoactive intestinal polypeptide elicited a marked secretion. CONCLUSIONS: Benzalkonium chloride treatment eliminated the ability of cholera toxin to induce intestinal secretion. Thus, all afferent fibers in the intramural secretory reflex activated by cholera toxin are probably conveyed via the myenteric plexus, which functions as the integrating center in the enteric nervous system. The Ussing chamber technique using stripped intestinal preparations cannot be used when studying effects of luminal secretagogues.
An intestinal natriuretic factor.
In 1975, reports were published that suggested that the gastrointestinal tract can "taste" the intake of sodium and in some unknown way influence the kidneys to increase sodium excretion. To test whether the intestine contained a natriuretic factor, intestinal tissue from cats was homogenized and fractionated by ultrafiltration to a molecular range of approximately 500-10,000 Da and separated by gel chromatography (Sephadex G25). The fractions were pooled into four large fractions that were assayed for "natriuretic" activity on anesthetized rats. The fraction containing the material with an apparent molecular mass of 500-1,000 Da augmented renal excretion of sodium and water, whereas the other pooled fractions did not exhibit any consistent natriuretic effect. The "natriuretic" fractions from gel filtration were further purified by ion exchange chromatography using a cation exchanger. The natriuretic activity was eluted from the ion exchange chromatography column at a NaCl concentration of 250 mM. Preliminary experiments on Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) suggest that the intestinal influence on renal sodium excretion is more pronounced in SHR than in WKY rats.
On the involvement of tachykinin neurons in the secretory nervous reflex elicited by cholera toxin in the small intestine.
The possible involvement of tachykinins in the nervous reflex activated by exposing the intestinal mucosa to cholera toxin was investigated in cats and rats. Three types of experiments were performed. In cats the release of tachykinins into blood was followed after placing cholera toxin in the intestinal lumen. In rat experiments a tachykinin receptor antagonist (Spantide II) was given close i.a. and its effect on cholera toxin-evoked fluid secretion was studied. Finally, in rats the effect of cholera toxin on the SP contents in the intestinal mucosa was studied. No release of tachykinins could be demonstrated. Spantide II did not change the rate of cholera toxin induced secretion. The SP content in the intestinal mucosa was not influenced by placing the toxin in the intestinal lumen. Hence, no experimental evidence was obtained for the involvement of a tachykinin neuron in the intestinal secretory nervous reflex activated by cholera toxin. Based on observations reported in the literature the involvement of an acetylcholine/tachykinin neuron in the reflex is tentatively discussed.
Effects of luminal stimuli on polyamine metabolism in the small intestine of the rat: the role of enteric nerves.
The aim of this study was to investigate to what extent polyamine metabolism in the small intestine of the rat is controlled by the enteric nervous system. Polyamine metabolism was followed by measuring the activity of ornithine decarboxylase (ODC) and in some instances also the content of polyamines (putrescine, spermidine and spermine). ODC activity in the intestine was increased when intraluminal pressure was increased and 3 h after placing cholera toxin in the intestinal lumen. Cholera toxin also increased the tissue putrescine content. Atropine or hexamethonium given i.v. did not influence the evoked changes of ODC activity. The pressure induced changes were not decreased by placing lidocaine on the serosal surface. On the other hand, the ODC activity of control segments were decreased by hexamethonium or atropine. The presence of glucose in the intestinal perfusate did not augment tissue ODC activity, neither did the heat stable enterotoxin from Escherichia coli (STa). It is concluded that the effect on polyamine metabolism evoked by luminal pressure or cholera toxin seems not to be mediated via nerves, while nerves seem to influence ODC activity during control conditions. The experiments with enterotoxins suggest that cAMP is the intracellular second messenger controlling intestinal ODC activity.
Nerve involvement in fluid transport in the inflamed rat jejunum.
Net fluid transport was measured in denervated jejunal segments of rats infected with larvae of Nippostrongylus brasiliensis. On days 6-9 after nematode inoculation, when the jejunal segment exhibited macroscopic and microscopic signs of inflammation, net fluid absorption was noticeably attenuated compared with control, and in eight of 26 experiments a net fluid secretion was seen. To determine whether enteric nerves participated in the response, intravenous hexamethonium (10 mg/kg body weight) was given or lidocaine (1% solution) was placed on the serosa of the intestinal segment. Both drugs significantly reduced fluid secretion or increased fluid absorption. The effect was more pronounced the lower the rate of fluid absorption or the higher the rate of fluid secretion. The inflammatory response influenced intestinal fluid transport partly via activation of the enteric nervous system. It was estimated that 50-60% of the change in fluid transport caused by the parasite could be ascribed to activation of intramural nervous reflexes. The effect of hexamethonium indicates that a cholinergic synapse is present in the secretory nervous reflux activated by inflammation. Experiments were also performed on animals on days 11-14 after infection when the nematodes had been expelled from the animal. A large net fluid absorption was then recorded.
Actions of serotonin antagonists on cholera-toxin-induced intestinal fluid secretion.
The effects of several 5-hydroxytryptamine (5-HT) receptor antagonists were tested in rats in vivo on the intestinal fluid secretion evoked by cholera toxin. Five receptor antagonists were used, namely 2-bromolysergic acid diethylamine (2-bromo-LSD), granisetron, ketanserin, methysergide and ondansetron. The drugs were used in doses that inhibited the arterial hypertension and/or bradycardia evoked by 5-HT given i.v. Granisetron and ondansetron markedly diminished cholera-toxin-evoked secretion, whereas ketanserin was without any effect. Methysergide also diminished cholera-toxin-induced fluid secretion particularly when the drug was given as an i.v. infusion. The results are considered in relation to the pathophysiology of cholera secretion and to the current views of receptor subtypes for 5-HT. It is proposed that the receptor involved is a 5-HT3 receptor, possibly also a receptor of the 5-HT1 type. Results from experiments in which 5-HT (20 mM) was placed in the intestinal lumen to evoke an intestinal secretion suggest that the 5-HT3 receptor is located in the villus tissue. It was also demonstrated that zimeldine, an inhibitor of presynaptic 5-HT reuptake, diminished choleraic secretion, an effect that may be ascribed to a 5-HT tachyphylaxis caused by an accumulation of 5-HT in a synaptic cleft.
Neuroimmune modulation of epithelial function. An overview.
Explore the source record for details and available documents.