Biomedical subjects

L Fändriks

Publications and source records attributed to L Fändriks.

At least 37 records · Page 2Linked to original sources

PubMed2000

Conceivable mechanisms by which Helicobacter pylori provokes duodenal ulcer disease.

A conceivable concept for the development of duodenal ulcers in Helicobacter pylori (H. pylori) infected subjects is presented in this chapter. The concept includes an explanation of the fact that only a minority of all H. pylori-infected subjects will develop a duodenal ulcer. Helicobacter pylori infection of the antrum induces a hypersecretion of gastric acid secretion, giving rise to gastric metaplasia in the duodenal bulb. This gastric metaplasia is a prerequisite for H. pylori colonization of the bulb. These events are common to all H. pylori-infected subjects. However, a much higher density of H. pylori bacteria and colonization with virulent organisms has been found in the bulb of duodenal ulcer patients, resulting in a much stronger inflammatory reaction with active duodenitis and an impaired bicarbonate secretion. These characteristics, together with acid hypersecretion, seem to be the important factors in evoking a duodenal ulcer.

Antigens, Bacterial↗

PubMed2000

Intragastric CO2 and nitric oxide participate in the regulation of peptone-induced gastrin release in humans.

BACKGROUND: Moderate acidification of the gastric lumen inhibits peptone-induced gastrin release. The aim of the present study was to investigate if the gastric acid neutralization products CO2 (from secreted HCO3) and NO (from reduced salivary nitrite) could act as intermediate messengers between luminal acidity and the inhibition of peptone-induced gastrin release. METHODS: Fourteen healthy volunteers (mean age, 27 years; range, 20-39 years; 3 women) participated in the study. Intragastric perfusion with saline or peptone was performed on the healthy volunteers. Venous blood samples were analyzed for serum gastrin concentrations. Intragastric NO was measured by chemiluminescence. RESULTS: Basal serum gastrin ranged between 11 and 23 pmol/l. Peptone in Sörensen's phosphated buffer (pH 6.9, PCO2 0 mmHg) increased serum gastrin by 83% +/- 23%, whereas acidified peptone (pH 2.0) did not stimulate gastrin release. Acidified peptone buffered with NaHCO3 to neutrality (pH 6.9, PCO2 approximately 600 mmHg) increased serum gastrin by 166% +/- 29%. Low intragastric NO levels were obtained by deviation of saliva. During such salivary depletion, acidified peptone (pH 2.0) stimulated gastrin release to a level of about 40% of the control response (pH 6.9). This peptone-induced gastrin response during salivary deviation was inhibited by addition of nitrite to the perfusate. CONCLUSIONS: Acid-induced inhibition of peptone-stimulated gastrin release is partly dependent on intraluminal NO formed in the reaction between salivary nitrite and gastric acid. In addition, the gastric acid neutralization product CO2 seems to potentiate the effect of peptone on gastrin release.

Adult↗

PubMed2000

Specific angiotensin II receptor blockage improves intestinal perfusion during graded hypovolemia in pigs.

OBJECTIVE: To investigate the potential of specific angiotensin II subtype 1 (AT1) receptor blockade to modify the mesenteric hemodynamic response to acute hypovolemia and retransfusion. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University-affiliated animal research laboratory. SUBJECTS: Fasted, anesthetized, ventilated, juvenile domestic pigs of both sexes. INTERVENTIONS: Acute, graded hypovolemia by 20% and 40% of the total estimated blood volume followed by retransfusion in control animals (CTRL; n = 10) and animals pretreated with the AT1 receptor blocker candesartan (CAND; n = 10). MEASUREMENTS AND MAIN RESULTS: Invasive monitoring of arterial and central venous blood pressures, cardiac output, portal venous blood flow, and jejunal mucosal blood flow. Blood gases were repeatedly analyzed to calculate oxygen delivery and consumption. Thirty minutes after each level of hypovolemia at 20% and 40%, cardiac output was decreased in CTRL animals from a baseline of 2.9 +/- 0.1 to 1.8 +/- 0.2 and 1.1 +/- 0.2 L/min, with no differences compared with CAND animals. Cardiac output was restored to 3.0 +/- 0.3 L/min 30 mins after retransfusion in CTRL animals, with no significant intergroup differences. Baseline portal venous blood flow (Q(MES)) and jejunal mucosal perfusion (PU(JEJ)) were greater in CAND animals compared with CTRL animals. During graded hypovolemia, CAND animals maintained Q(MES) and PU(JEJ) at significantly higher levels compared with CTRL animals, particularly after 40% hemorrhage (+221% and + 244%, respectively, relative to the mean values in CTRL animals). The same pattern was observed after retransfusion. Moreover, the calculated mesenteric critical oxygen delivery was significantly greater in CTRL animals (74 mL/min) compared with CAND animals (34 mL/min). No animals died in the CAND group, whereas four animals died during 40% hypovolemia or retransfusion in the CTRL group. CONCLUSIONS: Specific AT1 blockade before acute hypovolemia significantly ameliorated mesenteric and, in particular, jejunal mucosal hypoperfusion. In addition, cardiovascular stability was improved, and mortality in conjunction with acute hypovolemia and retransfusion could be completely avoided. These findings support a fundamental role of the renin-angiotensin system in the mesenteric response to acute hypovolemia and indicate a substantial interventional potential for candesartan in conjunction with circulatory stress.

Acid-Base Equilibrium↗

PubMed2000

Jejunal mucosal nitric oxide production and substrate dependency during acute mesenteric hypoperfusion in pigs.

OBJECTIVE: Jejunal nitric oxide (NO) formation is impaired during mucosal hypoperfusion. This study was undertaken to investigate whether this phenomenon could result from a restricted mucosal availability of NO-synthase substrates, ie, oxygen and/or L-arginine. DESIGN: Controlled study using laboratory animals. SETTING: University animal research laboratory. SUBJECTS: Eighteen chloralose-anesthetized, ventilated, juvenile Landrace domestic pigs. INTERVENTIONS: Mesenteric hypoperfusion was induced by intrapericardial infusion of Ringer's solution to achieve decreased cardiac output by creation of cardiac tamponade. MEASUREMENTS AND MAIN RESULTS: Animals were prepared for jejunal intraluminal perfusion with 150 mM NaCl or 3 mM L-arginine solution in an isolated intestinal segment and then subjected to cardiac tamponade. Jejunal mucosal NO formation was measured with a tonometric technique. Mesenteric blood flow was measured as portal blood flow, and mucosal perfusion was measured by laser Doppler flowmetry. Regional oxygen consumption and delivery were calculated from arterial and portal blood samples. Cardiac tamponade reduced jejunal NO formation (-52%), mesenteric oxygen delivery (-75%), oxygen consumption (-39%), and mucosal perfusion (-43%). Oxygenation of the jejunal intraluminal perfusate completely restored the intestinal NO levels within 30 mins, whereas presence of L-arginine was without effect. CONCLUSIONS: The study indicates that oxygen rather than L-arginine is the rate-limiting factor for mucosal NO production during acute reduced splanchnic perfusion.

Animals↗

PubMed2000

Angiotensin II blockade in existing hypovolemia: effects of candesartan in the porcine splanchnic and renal circulation.

Angiotensin II (AngII) is an important vasoconstrictor during hypovolemia. This study focused on the effects of the AngII receptor blocker candesartan on intestinal, hepatic, and renal hemodynamics during severe hypovolemia when administered in preexisting moderate hypovolemia. It was hypothesized that specific AngII receptor blockade might enhance splanchnic perfusion during hypovolemia. Fasted, anesthetized, ventilated, juvenile pigs were hemorrhaged by 20% of the blood volume for 30 min. Animals were then randomized to receive candesartan (CAND, n = 11) or the vehicle (CTRL, n = 10) prior to further hemorrhage to 40% of the blood volume for 30 min. The shed blood was then retransfused. Systemic and splanchnic hemodynamics were recorded including intestinal mucosal, superficial and parenchymal hepatic, and cortical and medullary renal microcirculation by laser-Doppler flowmetry. Arterial blood gases were analysed. Candesartan-treated animals maintained mesenteric and jejunal mucosal perfusion during 40% hypovolemia compared to CTRL animals, while no differences were observed in the hepatic and renal circulation. Retransfusion restored mesenteric and renal blood flows despite persistent hypotension and reduced cardiac output in both CAND and CTRL animals. Renal medullary and hepatic parenchymal microcirculation failed to recover during retransfusion in both CAND and CTRL animals. Arterial acidosis, hypercarbia, and a negative base excess were observed in CTRL animals following retransfusion whereas those parameters were normalised in CAND animals. Administration of candesartan in moderate hypovolemia ameliorated the reduction and consequences of mesenteric and intestinal, but not hepatic perfusion during severe hypovolemia. No adverse effects were observed in the renal circulation.

Acid-Base Equilibrium↗

PubMed1999

Differentiation of the peptidergic vasoregulatory response to standardized splanchnic hypoperfusion by acute hypovolaemia or sepsis in anaesthetized pigs.

This study was performed to integratively investigate the vasoregulatory response during standardized splanchnic hypoperfusion in pigs. Splanchnic perfusion was reduced to 50% of baseline by: haemorrhage by 20 and 40% of the estimated total blood volume; femoral venous infusion of live E. coli to establish sepsis of systemic origin; portal venous infusion of live E. coli to establish sepsis of splanchnic origin. Invasive haemodynamic monitoring and radioimmunoassay analyses of arterial plasma concentrations of angiotensin II, endothelin-1 and atrial natriuretic peptide were carried out. Acute hypovolaemia reduced systemic and splanchnic vascular resistances following transient increases and increased angiotensin II levels (+587%), whereas endothelin-1 and atrial natriuretic peptide levels did not change significantly. Systemic sepsis following femoral venous infusion of E. coli resulted in increased splanchnic vascular resistance and increased levels of angiotensin II (+274%), endothelin-1 (+134%) and atrial natriuretic peptide (+185%). Infusion of E. coli via the portal venous route induced an increase in splanchnic vascular resistance associated with particularly elevated levels of angiotensin II (+1770%) as well as increased endothelin-1 (+201%) and atrial natriuretic peptide (+229%) concentrations. Hypovolaemia and sepsis, although standardized with a predefined level of splanchnic hypoperfusion, elicited differentiated cardiovascular and vasopeptidergic responses. Sepsis, particularly of portal origin, notably increased splanchnic vascular resistance related to increased production of the vasoconstrictors angiotensin II and endothelin-1. The role of atrial natriuretic peptide as a vasodilator seems to be of subordinate importance in hypovolaemia and sepsis.

Acute Disease↗

PubMed1999

Is the esophageal squamous epithelial barrier function impaired in patients with gastroesophageal reflux disease?

BACKGROUND: A disturbed epithelial barrier function has been promoted as one factor in the pathogenesis of gastroesophageal reflux disease (GERD). We therefore studied the effect of acid perfusion on the transmural potential difference (PD) of the distal esophagus in relation to onset of reflux symptoms. METHODS: PD was assessed during perfusion with saline and with 0.1 M HCl in healthy controls (n = 17) and in GERD patients without (n = 15) or with esophagitis (n = 6) and in remission after a fundoplication (n = 10). Heartburn and other upper GI symptoms were recorded concomitantly. Endoscopy-negative patients were studied before and after omeprazole treatment. RESULTS: HCl perfusion induced more lumennegative peak PD values in patients with active GERD, regardless of the presence or absence of esophagitis, than in healthy controls. After successful therapy, the PD response to acid perfusion equalled that of healthy subjects. Acid perfusion was associated with the onset of heartburn in most patients with active GERD but in none of the healthy subjects, and less frequently after medical and surgical therapy. CONCLUSIONS: The epithelial permeability to hydrogen ions differs between healthy subjects and patients with active GERD. Effective treatment, such as omeprazole or fundoplication, might improve the barrier function.

Adolescent↗

PubMed1999

Splanchnic circulation and regional sympathetic outflow during peroperative PEEP ventilation in humans.

The splanchnic organs represent a major target for sympathetic outflow and an important region for haemodynamic effects on cardiovascular homeostasis. We have studied regional haemodynamic and sympathetic changes in the splanchnic bed during standardized circulatory stress from positive end-expiratory pressure ventilation (PEEP). We investigated eight patients undergoing major upper abdominal surgery using a radiotracer method to measure plasma spillover of norepinephrine as an index of sympathetic nerve activity using arterial, portal and hepatic venous blood sampling. Mesenteric and hepatic perfusion were measured by ultrasound transit time flowmetry and blood-gas analyses. Steady state measurements were performed before and during PEEP ventilation at 10 cm H2O. Plasma spillover of norepinephrine in the mesenteric and hepatic organs represented mean 49 (SEM 8)% and 7 (2)%, respectively, of systemic norepinephrine spillover at baseline, and PEEP ventilation did not cause any significant changes. However, PEEP ventilation significantly decreased portal venous blood flow while hepatic blood flow was preserved by a compensatory increase in hepatic arterial blood flow. Mesenteric and hepatic oxygen delivery changed according to blood flow, and there were no changes in regional oxygen consumption. Thus PEEP ventilation altered mesenteric and hepatic perfusion, independent of any change in corresponding sympathetic nerve activity. Regulation of hepatic blood supply, not related to sympathetic activity, maintained liver oxygenation during PEEP ventilation despite a simultaneous decrease in mesenteric perfusion.

Adult↗

PubMed1998

Carbon dioxide mediates duodenal mucosal alkaline secretion in response to luminal acidity in the anesthetized rat.

BACKGROUND & AIMS: Acid exposure of the duodenum elicits various functional responses, e.g., an increased mucosal alkaline secretion. Despite low pH in luminal contents, the mucosal secretion of bicarbonate-rich fluid results in pH neutrality at the surface epithelium. It follows that it is probably not luminal pH that triggers the secretory response. The present study was undertaken to investigate if CO2 could serve as an intermediate messenger between luminal acid and the mucosal secretory response. METHODS: Experiments were performed on chloralose-anesthetized rats. The duodenal mucosal alkaline secretion was measured by in situ pH-stat titration. RESULTS: Exposure of the duodenal mucosa to CO2, administered either as a pregassed solution (pH 4, PCO2 700 mm Hg) or as an acidified bicarbonate solution (pH 6.4, PCO2 240 mm Hg), raised the alkaline output by approximately 65%. This response was blocked by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (0.3 mmol/L intraluminally) but not by indomethacin (5 mg/kg intravenously). CONCLUSIONS: Exposure of the duodenal mucosa to solutions with high concentrations of CO2 increases the mucosal alkaline secretion despite an almost neutral pH. Data indicate that the L-arginine/NO pathway is involved in the mediation of this response.

Animals↗

PubMed1998

Acid-induced duodenal mucosal nitric oxide output parallels bicarbonate secretion in the anaesthetized pig.

We recently showed the involvement of the L-arginine/nitric oxide (NO) pathway in acid-induced duodenal mucosal bicarbonate secretion in rats. The aim of the present study was to confirm this observation in pigs by direct measurements of NO production. Experiments were performed on 16 anaesthetized pigs of both sexes treated with guanethidine (6 mg kg-1, intravenously). A duodenal segment, devoid of pancreaticobiliary influxes, was perfused with saline and the duodenal mucosal bicarbonate secretion was calculated from continuous measurements of pH and PCO2. The perfusate contents of NO and its oxidative product nitrite were determined by chemiluminescence, after reduction of nitrite to NO. Luminal acidification with 30 mM hydrochloric acid increased the output of bicarbonate as well as NO to the perfusate, by 195 +/- 45% and 106 +/- 10%, respectively. These responses to acid were markedly inhibited by adding the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 0.3 mM) to the perfusate. The inhibitory effect of L-NMMA could be reversed by administration of L-arginine (3 mM). The study presents simultaneous measurements of bicarbonate and NO outputs to a duodenal luminal perfusate. The results strongly support the view that the L-arginine/NO pathway is involved in the acid-induced duodenal mucosal bicarbonate secretory response.

Anesthetics, Combined↗

PubMed1998

Detecting gastrointestinal hypoperfusion during cardiac tamponade in pigs: a role for nitric oxide tonometry?

OBJECTIVE: To evaluate different techniques and regional approaches for detecting critical reductions in gastrointestinal (GI) perfusion. DESIGN: Laboratory, animal, controlled study. SETTING: University animal research laboratory. SUBJECTS: Thirteen anesthetized, ventilated, juvenile domestic pigs. INTERVENTIONS: Dextran was infused into the pericardial sac to achieve cardiac tamponade that reduced cardiac output to 25% of baseline value. Hemodynamics were invasively monitored, and blood gases were sampled in the systemic and portal circulations. Tonometers were placed in the corpus of the stomach and in the jejunum, 50 cm aboral to the ligament of Treitz. MEASUREMENTS AND MAIN RESULTS: We measured cardiac output, portal venous blood flow, mesenteric oxygen delivery and consumption, systemic and portal venous blood gases and acid-base balance, stomach and jejunal transepithelial potential difference, stomach and jejunal intramucosal pH, arterial plasma concentrations of asymmetric dimethylarginine, and jejunal, intraluminal nitric oxide. One hour of cardiac tamponade decreased mesenteric oxygen delivery and consumption in a linear fashion and resulted in mesenteric acidosis, as evidenced by decreases in pH, standard bicarbonate, oxygen saturation, and PO2 and increases in PCO2. The potential difference in the jejunum decreased earlier than in the stomach, whereas stomach intramucosal pH decreased before jejunal intramucosal pH. Intraluminal nitric oxide in the jejunum was markedly reduced soon after cardiac tamponade. This reduction was accompanied by an increase in arterial plasma concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine. Investigated variables were unchanged in control animals. CONCLUSIONS: Both intramucosal pH and potential difference measurements may be used to detect critical reduction in GI perfusion. Regional and temporal differences may reduce the accuracy of these methods. Jejunal tonometry can yield an early nitric oxide measurement that indicates mesenteric low-flow conditions. Jejunal tonometry also yields quantitative information about this modulator of hemodynamic and mucosal barrier function, information that is relevant to GI failure during shock.

Acid-Base Equilibrium↗

PubMed1998

Human duodenogastric reflux, retroperistalsis, and MMC.

The aim of this study was to determine to what extent human migrating motor complex (MMC)-related secretory phenomena are influenced by a recently discovered period of duodenal retroperistalsis during late phase III. A constant-flow perfusion technique was used to measure gastric appearance of acid, bicarbonate, pepsin, bilirubin, IgA, and duodenally infused [14C]polyethylene glycol (PEG) 4000 in 12 healthy volunteers. Interdigestive gastroduodenal motility was recorded by digital manometry. During late antral phase II and III, the gastric lumen was acidified (P < 0.005 phase III vs. phase I) together with a marked increase in luminal pepsin output (3.1 +/- 1.2 during phase III vs. 0.25 +/- 0.08 kU/5 min in phase I, P < 0.01), followed by a realkalinization due to a simultaneous reduction of acid secretion and a duodenogastric reflux, aided by retrograde peristalsis, of bicarbonate and IgA but not of bilirubin, at the end of antral phase III (P < 0.05 phase III vs. phase I values). This physiological duodenoantral reflux phenomenon may play an important role in the chemical and immunological restitution of the antral mucosal barrier function after the exposure to high acid and pepsin concentrations during antral phase III activity.

Adult↗

PubMed1997

ACE inhibition by enalaprilate stimulates duodenal mucosal alkaline secretion via a bradykinin pathway in the rat.

The effects of enalaprilate on duodenal mucosal alkaline secretion (in situ titration) and mean arterial blood pressure were investigated in chloralose-anesthetized male rats. A bolus injection of enalaprilate (0.7 mg/kg intravenously) increased alkaline secretion by about 60%, and this response was resistant to guanethidine (5 mg/kg intravenously), splanchnicotomy, and vagotomy. Furthermore, angiotensin II infusion (0.25-2.5 microg/kg/hr intravenously) following the administration of enalaprilate failed to influence this response. Bradykinin (10(-6)-10(-4) M) applied topically to the serosal surface of the duodenal segment under study increased dose-dependently the duodenal mucosal alkaline secretion, an effect that could be blocked by the selective bradykinin receptor subtype-2 antagonist HOE140 (100 nmol/kg intravenously). HOE140 also antagonized the response to enalaprilate. These data suggest that enalaprilate increases duodenal mucosal alkaline secretion via a local bradykinin pathway involving receptors of the bradykinin receptor subtype-2 antagonist, rather than by blockade of endogenous angiotensin II or by central autonomic neural regulation.

Adrenergic beta-Antagonists↗

PubMed1997

Acid-induced increase in duodenal mucosal alkaline secretion in the rat involves the L-arginine/NO pathway.

Duodenal mucosal alkaline secretion increases in response to hydrochloric acid exposure. The tentative role of nitric oxide (NO) in the mediation of this response was investigated. The mucosal alkaline output by a duodenal segment was recorded by in situ titration in chloralose-anaesthetized rats. In some experiments the duodenal blood flow was estimated by laser-Doppler flowmetry. Exposure of the duodenum to acid (0.01 M HCl, 5 min) increased the alkaline secretion by approximately 85%. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 10 mg kg-1 intravenously or 0.3 mM intraluminally) blocked the secretory increment after mucosal acid exposure. Mean arterial pressure and basal alkaline secretion were markedly raised, whereas duodenal blood flow was decreased, when L-NAME was given intravenously (i.v.). Intraluminal (i.l.) administration left mean arterial pressure as well as duodenal blood flow unaltered, and the duodenal mucosal alkaline secretion was only slightly elevated. The stereoisomer NG-nitro-D-arginine methyl ester (D-NAME) had no effect on either basal or acid-induced duodenal alkaline output. In animals receiving L-arginine (10 mg kg-1 min-1 i.v., or 3 mM i.l.) and L-NAME, the acid exposure elicited an increase in duodenal mucosal alkaline secretion, similar to that observed in controls. The results suggest that the acid-induced increase in duodenal mucosal alkaline secretion involves NO synthesis, which takes place close to the lumen, probably within the mucosa.

Animals↗

PubMed1997

Water extract of Helicobacter pylori inhibits duodenal mucosal alkaline secretion in anesthetized rats.

BACKGROUND & AIMS: The pathophysiology behind Helicobacter pylori-induced gastroduodenal dysfunction is incompletely understood. The aim of this study was to investigate if a water extract of H. pylori distorts acid-induced duodenal mucosal alkaline secretion. METHODS: Chloralose-anesthetized rats were prepared for duodenal luminal perfusion and in situ pH-stat titration of mucosal alkaline secretion. RESULTS: Mucosal bicarbonate secretion increased approximately 55%-60% after a 5-minute exposure to 10 mmol/L HCl. This response was absent when water extracts of three strains of H. pylori (protein content, 0.2-20 microg/mL) had been added to the perfusate. Presence of 3 mmol/L L-arginine, but not the stereoisomer D-arginine, in the luminal perfusate reversed the H. pylori extract blockade of acid-induced mucosal alkaline secretion. High-performance liquid chromatography-based analyses showed that the endogenous nitric oxide synthase inhibitor asymmetric dimethyl arginine (ADMA) increased fourfold in duodenal perfusate and fivefold in duodenal tissue after H. pylori extract exposure. In vitro proteolysis of H. pylori extract also resulted in a substantial accumulation of ADMA. Exogenously administered ADMA, giving similar tissue concentrations, inhibited the mucosal alkaline response to acid exposure. CONCLUSIONS: Water extracts of H. pylori inhibit acid-induced mucosal alkaline secretion via interference with mucosal NO synthase.

Anesthesia↗

PubMed1997

Sympathetic and renin-angiotensin activation during graded hypovolemia in pigs: impact on mesenteric perfusion and duodenal mucosal function.

Sympathetic and angiotensinergic activation reduce splanchnic oxygen delivery during hypovolemia, which may lead to failure of the intestinal mucosal barrier and eventually multiple organ dysfunction. This study integrates sympathetic and angiotensinergic responses with splanchnic hemodynamics and duodenal mucosal function during hypovolemia and evaluates pharmacologic blockade of either system to ameliorate the impact of acute hypovolemia. Chloralose-anesthetized pigs subjected to 20 and 40% blood volume reductions were randomized to controls or administered guanethidine or enalaprilate to block sympathetic and angiotensinergic activation, as assessed by plasma norepinephrine spillover and angiotensin II levels, respectively. Mesenteric and hepatic oxygen delivery/consumption as well as duodenal mucosal alkaline secretion and potential difference were determined. Hypovolemia preferentially increased mesenteric sympathetic outflow and caused a vigorous angiotensinergic activation. Guanethidine and enalaprilate blocked effectively the sympathetic and angiotensinergic responses. Treatment with enalaprilate, but not guanethidine, prevented the reduction of mesenteric oxygenation and duodenal mucosal alkaline secretion and potential difference observed in control animals. The down-regulation of mesenteric oxygenation and duodenal mucosal function during hypovolemia can be prevented by administration of enalaprilate, whereas guanethidine is uneffective in this respect. Interference with the reninangiotensin system might be of clinical interest to support mesenteric perfusion and organ function in hypovolemia.

Angiotensin II↗

PubMed1997

Hemodynamic, sympathetic and angiotensin II responses to PEEP ventilation before and during administration of isoflurane.

BACKGROUND: Positive end-expiratory pressure (PEEP) ventilation and isoflurane anesthesia may opposingly affect the sympathetic nervous and renin-angiotensin systems. This study was performed to elucidate the modulatory effects of isoflurane anesthesia on the neurohumoral and cardiovascular responses to PEEP. METHODS: Renin-angiotensin and sympathetic nervous activity were investigated in mechanically ventilated, normovolemic, chloralose anesthetized pigs before and during administration of 1.4% isoflurane. Arterial angiotensin II (AII) concentrations were measured and systemic, mesenteric, hepatic and renal spillover of norepinephrine (NE-SO) were calculated using isotope dilution. Regional hemodynamic variables were investigated in parallel. RESULTS: PEEP10 alone moderately elevated AII levels (+12.5 +/- 4.9 pg/ml, P < 0.05) and increased systemic (+22 +/- 2.9 pmol.min.100 g-1, P < 0.05) and notably mesenteric (+32 +/- 9.6 pmol.min.100 g-1, P < 0.05) NE-SO. Blood flow decreased in all vascular beds studied. Except for in the liver, isoflurane generally reduced NE-SO compared to baseline but did not change AII concentrations. Strikingly, the sympathoexcitatory response to PEEP10 was inhibited, whereas AII increased markedly (+284 +/- 64 pg/ml, P < 0.05) during PEEP10 and isoflurane. Renal blood flow was significantly more reduced during PEEP10 and isoflurane compared to PEEP10 alone, whereas the magnitude of reductions were similar in the other vascular beds. CONCLUSION: The data suggest that renin-angiotensin activation is important to attenuate the impact of PEEP ventilation on cardiovascular performance during administration of the sympathodepressant isoflurane. Interference with the renin-angiotensin system may cause cardiovascular decompensation in isoflurane anesthetized patients subjected to PEEP-ventilation.

Anesthesia, Inhalation↗

PubMed1997

ANG II prolongs splanchnic nerve-mediated inhibition of duodenal mucosal alkaline secretion in the rat.

Hypovolemia inhibits duodenal mucosal alkaline (HCO-3) secretion by activation of sympathoadrenergic nerves. A possible involvement of the renin-angiotensin system was investigated. Experiments were performed on chloralose-anesthetized rats. The mucosal alkaline output by a duodenal segment was measured using in situ pH-stat titration equipment. A modest hypovolemia was induced by bleeding the animals approximately 10% of the total blood volume. This procedure decreased duodenal mucosal alkaline secretion to a sustained level of approximately 50% of baseline and reduced mean arterial pressure by approximately 20 mmHg. Intravenous pretreatment with the angiotensin-converting enzyme (ACE) inhibitor enalaprilate (0.7 mg/kg) or the angiotensin II-receptor antagonist losartan (10 mg/kg) altered the response to hypovolemia to a transient one, and alkaline secretion returned to the control level within 40-50 min. When exogenous angiotensin II was administered intravenously (0.25 and 0.75 microgram.kg-1.h-1), a hypovolemia-induced sustained depression of the secretion was observed even during ACE inhibition. Direct electrical stimulation (3 Hz, 5 V, 5 ms, bilaterally) of the peripheral splanchnic nerves decreased duodenal mucosal alkaline secretion to approximately 60% of the control level and increased mean arterial pressure by approximately 20 mmHg. However, in enalaprilate-pretreated animals, the inhibition of alkaline secretion due to splanchnic nerve stimulation was transient, a response that became sustained on angiotensin II substitution. These results suggest that the renin-angiotensin system prolongs the sympathoadrenergic inhibition of duodenal mucosal alkaline secretion and that angiotensin II, in this regard, acts mainly on the peripheral sympathetic efferents.

Angiotensin II↗