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Biomedical subjects

O Lundgren

Publications and source records attributed to O Lundgren.

At least 19 recordsLinked to original sources
PubMed1999

Lithium evokes a more pronounced natriuresis when administered orally than when given intravenously to salt-depleted rats.

The effects on renal sodium excretion of giving lithium chloride (LiCl; 0.75 mmol per kg body mass) by gavage or intravenously were investigated. The experiments were carried out on Wistar-Kyoto (WKY) or spontaneously hypertensive (SHR) rats in metabolic cages. The rats had been on a low-salt diet for 4 days. Urine excretion of water, sodium and potassium was followed before and for 24 h after giving LiCl. An oral dose of LiCl evoked a more pronounced renal sodium excretion in either strain of rat as compared to that following intravenous administration, in agreement with previous observations of the effects of giving sodium chloride. Choline chloride (1.5 mmol per kg body mass) given by gavage to WKY rats or SHR evoked no change in the renal excretion of sodium. Based on the results of the present study and on observations reported in the literature, we propose that the intestinal tract contains a sodium "sensor", which upon activation releases a natriuretic factor to cause renal sodium excretion. The present results indicate that the proposed "sensor" is sensitive to lithium but not chloride ions.

Administration, Oral↗
PubMed1999

Involvement of serotonin and calcium channels in the intestinal fluid secretion evoked by bile salt and cholera toxin.

1. The enteric nervous system (ENS) is activated when exposing the intestinal mucosa to cholera toxin or certain bile salts. Cholera toxin stimulates ENS, at least in part, by the release of 5-hydroxytryptamine (5-HT) from the enterochromaffin cells. Calcium channel blockers of the L-type markedly attenuate the fluid secretion and the luminal release of 5-HT caused by cholera toxin. 2. The objective of the present study was to elucidate if sodium deoxycholate activated ENS in a similar manner as cholera toxin. Furthermore, the effect of several calcium channel blockers was tested on the fluid secretion caused by cholera toxin or bile salt. 3. Sodium deoxycholate (4 mM) caused a release of 5-HT into the intestinal lumen, which was inhibited by calcium channel blockade. Granisetron, a 5-HT3 receptor blocker, partly inhibited the fluid secretion caused by bile salt. 4. The effects of nifedipine, felodipine, R-felodipine, H186/86 (t-butyl analogue of felodipine) on the fluid secretion caused by cholera toxin or sodium deoxycholate were studied. Both secretory states were markedly attenuated in a dose dependent manner by all calcium channel blockers tested regardless of their effects on arterial pressure. 5. It is concluded that both cholera toxin and bile salt activate ENS, at least in part, via a release of 5-HT from the enterochromaffin cells. The antisecretory effect calcium channel blockers is partly explained by an inhibition of this release of 5-HT.

Animals↗
PubMed1999

The effects on net fluid transport of noxious stimulation of jejunal mucosa in anaesthetized rats.

A major aim of the present study was to investigate whether exposing the jejunal mucosa to a noxious stimulus induces a net fluid secretion by activating the enteric nervous system (ENS) and, if so, to what extent an axon reflex was involved. Net fluid transport was measured in vivo with a gravimetric method. The intestinal mucosa was exposed to an isotonic solution with an unphysiologically low pH (1.0). This evoked a fluid secretion, which was markedly attenuated by giving hexamethonium (nicotinic receptor antagonist) i.v. or exposing the intestinal serosa to lidocaine (local anaesthetic). Atropine (muscarinic receptor antagonist) had no effect. Luminal acid evoked a fluid secretion of the same magnitude in acutely denervated segments and in segments denervated about 3 weeks prior to the experiments. Luminal capsaicin (1.6-16 mM) did not influence jejunal net fluid transport. A second aim of the study is to investigate the effect of nifedipine (Ca channel blocker of L-type) on the acid-induced fluid secretion. Nifedipine markedly attenuated acid-induced fluid secretion. In contrast to cholera toxin-evoked secretion, the nifedipine effect was not mediated via 5 hydroxytryptamine (5-HT) as judged by measurements of 5-HT release into the intestinal lumen and the lack of effect of granisetron (5-HT3 receptor antagonist). It is concluded that the net fluid secretion evoked by hydrochloric acid in the small intestine is mainly mediated via an intramural reflex in the ENS. No experimental evidence was obtained for the involvement of an axon reflex. The site of action of the calcium channel blocker is tentatively discussed.

Anesthesia↗
PubMed1998

Nervous control of alkaline secretion in the duodenum as studied by the use of cholera toxin in the anaesthetized rat.

There is experimental evidence for an axon reflex control of alkaline secretion in the rat duodenum. We have investigated if there is also an intramural reflex control of alkaline secretion similar to that demonstrated with regard to the control of the fluid transport in the rat jejunum. Alkaline secretion in the duodenum of an anesthetized rat was continuously monitored using an in situ titration technique. The segment was extrinsically denervated. Exposing the duodenal segment to 80 microg cholera toxin markedly increased alkaline secretion. This response was abolished by hexamethonium (28 micromol (10 mg) kg(-1) body wt), a nicotinic receptor blocker, lidocaine (0.5 mL of a 1% solution on the serosal surface), a local anaesthetic, and nifedipine (5.75 micromol (2 mg) kg(-1) body wt i.v.), a calcium channel blocker. The response to cholera toxin was partially abolished by granisetron (0.11 micromol (40 microg) kg(-1) body wt i.v.), a 5-HT3 receptor blocker. Atropine (1.7 micromol (0.5 mg) kg(-1) body wt i.v.), a muscarinic receptor blocker, had no effect. We therefore conclude that the alkaline secretion in the rat jejunum evoked by cholera toxin exhibits the same pharmacological properties as the fluid secretion caused by the toxin in the jejunum. This suggests that the alkaline secretion in the rat duodenum is controlled not only by an axon reflex but also by an intramural secretory reflex similar to that controlling fluid transport in the rat jejunum.

Alkalies↗
PubMed1997

The effects of enalapril on the natriuretic response evoked by an oral sodium load in sodium deprived normotensive and hypertensive rats.

Previous studies have shown that an oral sodium load during sodium deprivation is excreted faster than an intravenous load. We wanted to study whether the renin-angiotensin-aldosterone system might be associated with this phenomenon and therefore the influence of the angiotensin converting enzyme (ACE) inhibitor enalapril was investigated. The experiments were performed on four strains of rat: spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) rats, inbred hypertension-prone (SS/Jr) and hypertension-resistant (SR/Jr) Dahl rats. In SHR and WKY rats pretreated with enalapril it was observed that an intravenous sodium load induced a renal sodium excretion which was between two and five times larger than that seen after an oral load. In SR/Jr and SS/Jr rats the sodium excretion was the same regardless of the route of administration. In SS/Jr rats sodium excretion increased three- to fourfold upon sodium repletion, whereas no significant increase was observed in SR/Jr rats. Thus, the present results indicate that an intact renin-angiotensin system is necessary for the interplay between the gastrointestinal tract and kidney.

Administration, Oral↗
PubMed1997

Effects of calcium channel blockade on intestinal fluid secretion: sites of action.

Most intestinal secretagogues, including cholera toxin, evoke fluid secretion in part by activating the enteric nervous system (ENS). The enterotoxins that, due to size, cannot pass the intestinal epithelial lining have been proposed to activate the ENS via the release of amines/peptides from the intestinal endocrine cells. It has been shown that calcium channel blockers of the L-type attenuate intestinal fluid secretion. This study was performed on rat jejunal segments to elucidate where calcium channel antagonists interact with the secretory nervous reflex(es) of the ENS. In vivo, net fluid transport, transmural potential difference (PD) and luminal release of serotonin from the enterochromaffin cells were monitored before and after exposing the intestinal mucosa to cholera toxin (20 microg/mL) or the calcium ionophore A23187 (0.5 mM). In vitro, the effects of transmural electrical field stimulation (EFS) on short circuit current (SCC) was investigated using the Ussing chamber method. Cholera toxin and A23187 evoked a net fluid secretion, an increased PD and an augmented luminal release of 5-HT. These effects were markedly attenuated by giving the calcium channel blocker nifedipine i.v. (5.75 micromol kg(-1) body wt). On the other hand, nifedipine (0.02 mM) had no significant effect on the increased SCC caused by EFS in vitro. The results obtained in the in vivo experiments suggest that the nifedipine markedly attenuates the initial event in cholera toxin- and A23187-induced secretion, the release of amines and probably also of peptides from the intestinal endocrine cells. The in vitro experiments seem to exclude an effect of the calcium channel blockade on the efferent part of the secretory nervous reflex.

Animals↗
PubMed1997

Calcium channels and intestinal fluid secretion: an experimental study in vivo in rats.

Several mechanisms involved in nervous secretory reflex(es) of the enteric nervous system may be dependent on the flux of calcium across the plasma membrane, which may be controlled by voltage-gated calcium channels. In this study, we investigated the importance of plasma membrane calcium channels for intestinal fluid secretion. Two types of studies were performed, in which intestinal net fluid transport in anaesthetized rats was followed with a gravimetric method. First, the effects on intestinal fluid transport of placing A23187, a calcium ionophore, in the intestinal lumen was studied. A23187 induced in a dose-dependent manner a net fluid secretion, which was abolished by giving hexamethonium (10 mg kg(-1) body wt) i.v. or placing lidocaine (1% solution) on the intestinal serosa. Nifedipine (5.75 micromol kg(-1) body wt i.v.) also abolished the fluid secretion caused by the ionophore. In the second study, the effects of various calcium channel blockers (gadolinium chloride, nifedipine, verapamil) were tested on the cholera toxin-induced secretion. It was attenuated by luminal application of gadolinium chloride (1-10 mM) or nifedipine (10-200 microM). Intravenously administered nifedipine (2.5-5.75 micromol kg(-1) body wt) abolished cholera toxin-evoked secretion dose-dependently, whereas verapamil (0.05-1 micromol kg(-1) body wt) was without consistent effect. It is concluded that the fluid secretion evoked by placing A23187 in the intestinal lumen in vivo was induced via an activation of the enteric nervous system. Cholera secretion was attenuated or abolished by calcium channel blockers of the L- or N-type.

Anesthetics, Local↗
PubMed1995

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)

Animals↗
PubMed1995

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.

Administration, Oral↗
PubMed1995

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.

Animals↗
PubMed1995

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.

Animals↗