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O Lundgren

Publications and source records attributed to O Lundgren.

At least 19 recordsLinked to original sources
PubMed1992

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.

Animals↗
PubMed1991

Is there an intestinal natriuretic factor?

Intestinal tissue from cats was homogenized and fractionated by ultrafiltration to a molecular range of about 500-10,000 and separated by gel chromatography. The fractions from the gel filtrations were tested with regard to their ability to inhibit Na,K-ATPase as assayed with p-nitrophenylphosphate. The fractions that inhibited Na,K-ATPase were pooled and named pooled fraction 2. Pooled fraction 1 contained molecules larger, and pooled fraction 3 and 4 the molecules smaller, than pooled fraction 2. The four fractions were assayed for natriuretic 'activity' on anaesthetized rats. Administering pooled fraction 3 (no Na,K-ATPase-inhibiting activity) i.v. augmented renal excretion of sodium and water, whereas the other pooled fractions did not exhibit any consistent natriuretic effect. Cardiac ventricular tissue from cats was fractionated in the same manner as was done for the intestine. None of the cardiac fractions contained any natriuretic material. It is proposed that the cat small intestine contains a natriuretic factor.

Administration, Oral↗
PubMed1991

On the mechanisms of the basal alkaline secretion in the rat ileum in vivo.

Basal alkaline secretion of the denervated rat ileum was monitored by a pH-stat method. Changes of transepithelial electrical potential difference (PD) were also continuously registered. In other experiments net fluid transport was measured with a gravimetric method. The importance of the enteric nervous system for the recorded variables was investigated by giving i.v. hexamethonium, neuropeptide Y (NPY) or methionine-enkephalin or by stimulating electrically the mesenteric nerves surrounding the superior mesenteric artery. Alkaline secretion was inhibited by about 20% by mesenteric nerve stimulation or by neuropeptide Y (NPY) or met-enkephalin i.v. A somewhat greater inhibition (approximately 30%) of transepithelial electrical potential difference was elicited by the mesenteric nerve stimulation and NPY whereas met-enkephalin did not cause any transepithelial electrical potential difference change. Net fluid absorption was markedly diminished (by approximately 65-75%) by met-enkephalin but not by NPY. The cellular mechanisms underlying alkaline secretion were investigated by means of amiloride, SITS and acetazolamide. The basal alkaline secretion and transepithelial electrical potential difference were not influenced by 10(-3)M or 10(-4) SITS. In contrast 10(-3) M amiloride caused a significant increase of alkaline secretion but not of transepithelial electrical potential difference. A 35% reduction in the alkaline secretion but not transepithelial electrical potential difference was observed after acetazolamide had been given intravenously. A similar decrease was observed after giving hexamethonium. We conclude: (1) Enteric nerves are of comparatively small importance in controlling the ileal alkaline secretion recorded during basal conditions; (2) About 35% of the basal ileal alkaline secretion is carbonic anhydrase dependent. This mechanism is not influenced by nicotinic receptor blockade; (3) Under the present experimental conditions there may be an alkaline secretion which is concealed by a simultaneously operating Na+/H+ exchanger and; (4) No consistent quantitative correlation exists between alkaline secretion, transepithelial electrical potential difference and net field transport in the denervated rat ileum.

Acetazolamide↗
PubMed1991

Tissue osmolality in intestinal villi of four mammals in vivo and in vitro.

Using a freezing point depression method osmolality in the intestinal tissue of four mammals (gerbils, guinea-pigs, rabbits and rats) was estimated in vivo, during fluid transport from an isotonic electrolyte-glucose solution. Net fluid transport was also measured. In gerbils, guinea-pigs and rabbits tissue osmolality was also estimated during in vitro conditions. A marked hyperosmolality was observed in vivo in the upper parts of the villi of all four mammals studied. The tissue osmolality was significantly higher than that seen in the same species during in vitro conditions. A villus hyperosmolality was observed also in species which exhibited a net fluid secretion (guinea-pig, rabbit ileum), indicating that the fluid secretion emanated from the intestinal crypts. Based on the results of the present experiments and on observations made in earlier experiments performed on the cat, it is proposed that the villus hyperosmolality is created by a countercurrent multiplier present in the intestinal villus. The hyperosmolar compartment in the villus tissue creates the force that drives fluid from lumen to tissue.

Animals↗
PubMed1991

Influence of fibre diameter and probe geometry on the measuring depth of laser Doppler flowmetry in the gastrointestinal application.

The measuring depth of laser Doppler flowmetry (LDF) was studied in isolated segments of feline small intestine, using five probes having different fibre geometry, fibre core diameter and fibre centre separation. Recordings were made on the mucosal side at constant systemic blood pressure and venous outflow from the bowel segment. The insertion of a layer of unperfused intestine (average thickness 2.4 mm), between the probe and the perfused bowel wall, reduced the output signal from the flowmeter to an average of 42% of the initial value when a probe with large diameter fibres (700 microns) was used. No LD-signal was obtained through the unperfused tissue layer using the probes with small core diameter fibres (120 microns). Application of a mirror at the serosal surface opposite to the probe, resulted in an average increase of the output signal by 50% using the large fibre diameter probe, whereas no increase was observed with the small fibre probe. Probes based on intermediate fibre diameter and fibre centre separations, gave intermediate results in both experiments. It is concluded that the measuring depth of laser Doppler flowmetry in the gastrointestinal application is highly dependent on the fibre diameter and geometry of the probe. It is possible that, by taking into account these factors, probes may be constructed that are suitable for superficial and transmural measurements.

Animals↗
PubMed1990

Studies of cholera toxin-induced changes of alkaline secretion and transepithelial potential difference in the rat intestine in vivo.

A pH-stat technique was used to investigate the effects of cholera toxin (CT) on alkaline secretion from denervated intestines (jejunum, ileum, colon) in anaesthetized rats. Transepithelial potential difference (PD) was also followed in some experiments. CT, given intraluminally, caused a marked increase in jejunal alkaline secretion, whereas only a small effect was observed in the ileum and no apparent effect was noted in the proximal colon. The pronounced increase in jejunal alkaline secretion was found to be inhibited by 10-25% by hexamethonium (10 mg kg-1 body wt i.v.) and similarly by serosal application of lidocaine, whereas atropine (0.25 mg kg-1 body wt i.v.) had no effect. Thus the cholera toxin-induced alkaline secretion in the jejunum is attributed mainly to a non-nervous mechanism. The small effect of CT on ileal alkaline secretion observed in this study contrasts with the high ileal bicarbonate concentration reported in cholera by authors who estimated the concentration from the total carbon dioxide/bicarbonate contents. This discrepancy may be explained by a CT-evoked increased transport of the coupled Na+/H+ and Cl-/HCO3- exchangers, which cannot be measured with the pH-stat technique used in this study.

Animals↗
PubMed1990

Intestinal fluid transport in the small intestine of normotensive and spontaneously hypertensive rats: the importance of enteric nerves, chloride and bicarbonate secretion.

Fluid transport was studied in periarterially denervated jejunal segments of spontaneously hypertensive rats (SHR) of the Okamoto strain and as a control also in Wistar-Kyoto rats (WKR). In agreement with the findings of an earlier report a 'spontaneous' fluid secretion was observed in SHR whereas the intestinal segments of WKR absorbed fluid. The fluid secretion in SHR was inhibited by tetrodotoxin or lidocaine placed on the serosal surface of the intestinal segment under study. These observations confirm our earlier proposal that secretory nervous pathways in the enteric nervous system evoke the fluid secretion in SHR. In an attempt to analyse the cellular mechanisms that underlie the fluid secretion in SHR the animals were given loop diuretics in doses that evoked diuresis. No effect on intestinal fluid transport was seen in SHR or WKR. Furthermore, to study the importance of bicarbonate transport alkaline secretion was monitored with a pH-stat technique. In the initial part of the experiments the alkaline secretion in SHR and WKR was similar. In half of the SHR experiments alkaline secretion increased with time. This increase could be completely reversed with hexamethonium and atropine (only tested in three experiments). The time course of the alkaline and fluid secretion in SHR did not coincide, indicating that bicarbonate ion transport was not the major cause of fluid secretion in SHR. In agreement with this conclusion it was observed that acetazolamide (a blocker of carbonic anhydrase) did not influence rate of fluid transport in SHR or WKR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Renal function during reperfusion after warm ischaemia in rabbits: an experimental study on the possible protective effects of pretreatment with oxygen radical scavengers or lidoflazine.

Survival and renal function were studied after 60 min of renal ischaemia and contralateral nephrectomy in four groups of French loop rabbits. One group served as untreated control animals. The other groups were pretreated with superoxide dismutase (SOD) and catalase, lidoflazine or a buffered albumin solution containing mannitol, L-methionine and MgCl2. Six out of nine rabbits died during the 14-day follow-up period in the untreated control group, while the corresponding figure in each of the three treatment groups was one out of nine. Five of the rabbits that died exhibited azotaemia or hyperpotassaemia that could explain the death, while four died of non-renal related causes. In the surviving animals, no differences in serum creatinine, potassium and sodium concentration or urinary output of osmoles was observed between the four groups. The increase in serum creatinine of the French loop rabbits observed after 60 min of ischaemia was considerably less pronounced than the corresponding increase observed in New Zealand White rabbits, indicating that the kidneys of the former strain are more tolerant to ischaemia. A cardiomyodepressant factor could be demonstrated in the venous effluent from previously ischaemic kidneys. This release could not be prevented by pretreatment with SOD and catalase.

Animals↗
PubMed1990

On the role of vasoactive intestinal polypeptide and tachykinins in the secretory reflex elicited by chemical peritonitis in the cat small intestine.

Peritonitis induced by serosal application of 0.1 M hydrochloric acid causes net fluid secretion via the enteric nervous system. The aim of the present study was to investigate the roles of vasoactive intestinal peptide (VIP) and tachykinins in this reflex(es). The release of tachykinins (substance P [SP], neurokinin A [NKA], neuropeptide K [NPK]) and VIP into the mesenteric circulation, net fluid transport, intestinal blood flow and sometimes motility were recorded simultaneously in extrinsically denervated jejunal segments of the cat in vivo. The release of both VIP and NKA was increased upon application of HCl to the cat jejunal serosa. Tetrodotoxin, hexamethonium and methionine enkephalin inhibited both the induced VIP release and the secretory response. The increased release of NKA was unaffected by hexamethonium. We propose that the intramural secretory reflex evoked by acid application of the serosa consists of an 'afferent' tachykinin neuron, a cholinergic interneuron and an 'efferent' VIPergic neuron innervating the secretory enterocytes.

Animals↗
PubMed1990

Further studies of the changes in alkaline secretion, transepithelial potential difference and net fluid transport induced by the heat-stable enterotoxin of Escherichia coli (STa) in the rat jejunum in vivo.

A pH-stat technique was used to study the mechanisms underlying the intestinal alkalinization evoked by the heat-stable enterotoxin of Escherichia coli (STa) in the rat denervated jejunum in vivo. In addition, concomitant changes of transepithelial potential difference and fluid transport were also investigated. To test the possible involvement of the enteric nervous system in the STa-stimulated alkaline secretion and potential difference, the mesenteric nerves were electrically stimulated or neuropeptide Y or methionine-enkephalin was infused intravenously. None of these interventions inhibited to any large extent the STa-stimulated alkaline secretion, whereas a greater suppression was noted on the concomitantly increased potential difference. Furthermore, neuropeptide Y but not methionine-enkephalin significantly inhibited STa-induced jejunal fluid secretion although neuropeptide Y was without effect on basal fluid transport. It is concluded that the enteric nervous reflex(es) which are of significant importance in explaining STa-evoked fluid secretion plays a minor role in controlling alkaline secretion. Furthermore, alkaline secretion may not contribute to the increase in potential difference caused by STa Amiloride (10(-4) or 10(-3) M) had no effect on the STa-stimulated alkaline secretion, implying that some cellular mechanism other than an inhibition of Na+/H+ exchanger explains the observed response. Similarly, acetazolamide had no effect on the STa-stimulated alkaline secretion or potential difference, suggesting that the secreted alkaline is of extracellular origin rather than from the cellular metabolism in the enterocytes.

Animals↗
PubMed1990

Effects of heat-stable Escherichia coli enterotoxin on intestinal alkaline secretion and transepithelial potential difference in the rat intestines in vivo.

The effects of the heat-stable enterotoxin of Escherichia coli (STa) on intestinal alkaline secretion and transepithelial electric potential difference (PD) were investigated in vivo in denervated segments of rat jejunum, ileum, and proximal colon. STa caused a significant increase in alkaline secretion in the jejunum but not in the ileum or colon. The jejunal effect of STa may be ascribed to a stimulation of bicarbonate secretion and/or an inhibition of Na+/H+ exchange. With regard to PD, STa caused a marked rise in colonic PD, whereas only a small response was found in the jejunum. No effect on PD was seen in the ileum. Hexamethonium (10 mg/kg intravenously) significantly diminished the effects of STa on PD, whereas only a small inhibition of the STa-induced alkaline secretion was observed. The effect of lidocaine on PD and alkaline secretion was found to be similar to that of hexamethonium. Atropine had no effect on any of the studied variables. These findings suggest that STa exerts, via nerves, a profound influence on the jejunal transport mechanisms responsible for the changes in PD, whereas the influence on alkaline secretion is to a large extent not mediated via enteric nerves. Thus, the extent of enteric nervous control of epithelial function differs for different transport functions. The findings also indicate that the bicarbonate ion is not the anion mainly responsible for the fluid secretion elicited by STa.

Animals↗
PubMed1989

Effects of cholera toxin, Escherichia coli heat stable toxin and sodium deoxycholate on neurotensin release from the ileum in vivo.

Neurotensin (NT) is a biologically active peptide found in specialized epithelial cells (N-cells) in the distal small intestine. In this study we tested the hypothesis that NT may be released by luminal secretagogues, i.e., cholera toxin, Escherichia coli heat-stable toxin and sodium deoxycholate. Cholera toxin elicited net fluid secretion in anesthetized cats. This secretion was accompanied by an increased release of NT-like immunoreactivity (NTLI) into the mesenteric vein when NTLI was measured with either a C-terminally or a N-terminally directed antibody. An increasing plasma NTLI concentration (N-terminally directed antibody) was recorded in the mesenteric vein and femoral artery in cholera experiments. These results indicate that cholera toxin releases NT from the small intestine. Since neurotensin causes intestinal fluid secretion at least in part via an activation of enteric nerves we propose that the N-cell functions as a 'receptor cell' which activates an intramural secretory reflex upon luminal stimulation by cholera toxin. This study does not support a similar role for NT in the secretion elicited by the heat stable toxin of Escherichia coli or by sodium deoxycholate since we were unable to demonstrate any intestinal release of NTLI after exposing the intestine to these secretory agents.

Animals↗
PubMed1989

A swine model for studying intestinal circulation of the newborn.

We describe a newborn swine model to study intestinal hemodynamics of developing mammals. The preparation is designed to allow measurement of perfusion pressure and blood flow in an isolated segment of ileum under controlled conditions. Piglets in this study had a mean blood pressure of 65 +/- 14 (SD) mm Hg and mean intestinal blood flow of 80 +/- 20 (SD) ml/100 g/min at an average age and weight of 6.1 +/- 3 (SD) days and 1,718 +/- 427 (SD) g (n = 21). Experiments were performed to evaluate the effects of common physiologic perturbations: (a) Increased venous pressure caused a decrease in blood flow proportional to the lower perfusion pressure, but the relative change in vascular resistance was greater than the blood flow change. This effect, suggestive of a myogenic response, was significantly greater at a venous pressure increase of 20 cm of water over baseline compared with an increase of 10 cm water. (b) Gradual decrease in mesenteric artery blood pressure by clamping resulted in proportional decreases in blood flow. The calculated peripheral vascular resistance remained constant at blood pressure greater than 50 mm Hg and then increased as blood pressure decreased. (c) Stimulation of periarterial, postganglionic nerves surrounding the mesenteric artery produced a characteristic initial vasoconstriction followed by "autoregulatory escape." Frequency response tests using trains of stimulation of 6 ms and 12 V demonstrated responses starting at 2 Hz and maximal at 16 Hz. We suggest that this model should be applicable to a number of physiologic studies including assessment of water and nutrient flux in the intestine concomitant to changes in the circulation.

Animals↗
PubMed1989

Extravascular arteriovenous oxygen shunting in the cat stomach.

Venous appearance of oxygen and red cells labelled with methaemoglobin was compared in the gastric vascular bed. At 'resting' gastric blood flow the red cells appeared earlier than oxygen after simultaneous close i.a. injection, as would be expected from the intravascular laminar flow profile. However, when lowering arterial inflow pressure to the stomach by partially occluding the coeliac trunk, oxygen often appeared earlier than the red blood cells. When arterial pressure was lower than 50 mmHg this was always the case. This observation is taken to indicate that during these experimental conditions an extravascular shunting of oxygen occurs. It is suggested that this may occur in the submucosal vascular network and/or in the mucosa. The functional implications of such a mechanism are tentatively discussed.

Animals↗
PubMed1989

Evidence for an intramural nervous control of epithelial cell migration in the small intestine of the rat.

The migration of epithelial cells along the crypt-villus axis in the small intestine of the rat was followed by labelling epithelial cells during mitosis with [3H]thymidine given i.v. Using two different techniques (autoradiography and determination of tissue radioactivity) it was demonstrated that 6-9 h after giving the tracer the labelled cells had migrated longer in intestinal segments exposed to cholera toxin than in control segments. This effect of cholera toxin was abolished by giving hexamethonium. We have earlier shown that cholera toxin induces fluid secretion to a large extent by activating the enteric nervous system and we conclude from the present observations that cholera toxin in a similar fashion exerts a trophic effect on the intestinal epithelium via intramural nervous reflexes. The importance of co-release of several neurotransmitters in explaining the trophic effect is tentatively discussed.

Animals↗