Involvement of 5-HT3 and 5-HT4 receptors in the motor activity of isolated vascularly perfused rat duodenum

The involvement of serotonin (5-HT) receptor subtypes in motor activity of the ex vivo vascularly perfused rat duodenum was investigated. Clusters of phasic contractions (CPCs), migrating in an oral to anal direction, were obtained without any stimulation. Drug effects were evaluated by changes in different components of the pressure waves, such as motor index (MI), frequency, amplitude and duration of the CPC. The effect of 5-HT depletion on motor activity was examined in animals treated with p-chlorophenylalanine (PCPA). The MI, frequency and duration of CPC were decreased by PCPA, but the amplitude was not affected, suggesting that endogenous 5-HT may play an important role in regulation of the motor activity of the rat intestine. The importance of the 5-HT receptor subtypes in the regulation of motor activity was examined. Neither the nonselective 5-HT1 and 5-HT2 receptor antagonist, methysergide, nor the 5-HT2 receptor antagonist, ketanserin, affected motor activity. However, the 5-HT3 receptor antagonists, granisetron and azasetron, decreased percentage MI, frequency, percentage amplitude and percentage duration of CPC. The 5-HT4 receptor antagonist, SB204070, exerted both excitatory and inhibitory actions, with a higher dose (10 nM) stimulating percentage MI, frequency, percentage amplitude and percentage duration, and a lower dose (0.1 nM or 1 nM) decreasing percentage MI and percentage duration of CPC. These results suggest that endogenous 5-HT regulates the motor activity of the rat duodenum through 5-HT3 and 5-HT4 receptors, with the former mediating the stimulatory influence and the latter mediating both stimulatory and inhibitory influences.     

Motor activity of vascularly perfused rat duodenum. 2. Effects of VIP, PACAP27 and PACAP38

We examined the mechanisms of effects of vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase activating polypeptide (PACAP) 27 and PACAP38 on spontaneously occurring pressure waves in ex vivo perfused rat duodenum. VIP and PACAPs dose-dependently reduced the percentage motor index of pressure waves; this reduction was not prevented by atropine, hexamethonium or tetrodotoxin (TTX). VIP and PACAPs abolished acetylcholine-induced stimulation of pressure waves, even in the presence of TTX. These findings suggest that VIP and PACAPs may exert direct inhibitory effects via VIP/PACAP receptors located on smooth muscle rather than via cholinergic receptors. The inhibitory effects of VIP and PACAPs were partially antagonized by the VIP receptor antagonists VIP(10-28), suggesting that VIP and PACAPs share common receptor sites on intestinal smooth muscle. The effects of VIP and PACAPs were completely antagonized by nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NA), suggesting that NO mediates the inhibitory effects of VIP and PACAPs on duodenal motility. Furthermore, single injection of L-NA stimulated spontaneously occurring pressure waves, while VIP(10-28) did not affect them. These findings suggest that VIP/PACAPs and NO strongly interact as an inhibitory mediator on duodenal motility, but that their modes of action in doing so may differ.     

A quantitative approach to recording peristaltic activity from segments of rat small intestine in vivo

We have developed methods that allow correlation of propulsive reflexes of the intestine with measurements of intraluminal pressure, fluid movement and spatio-temporal maps of intestinal wall movements for the first time in vivo. A segment of jejunum was cannulated and set up in a Trendelenburg recording system while remaining connected to the vascular and nerve supply of the anaesthetized rat. The resting intraluminal pressure in intact intestine was 2-4 mmHg. Hydrostatic pressures of 2, 4, 8 and 16 mmHg were imposed. At a baseline pressure of 4 mmHg, propulsive waves generated pressures of 9 +/- 1 mmHg, that progressed oral to anal at 2-5 mm s(-1). Individual propulsive waves propelled 0.8 +/- 0.4 mL of fluid. The frequency of propulsive waves increased with pressure, but peristaltic efficiency (mL per contraction) decreased with pressure increase between 4 and 16 mmHg. Atropine, as a bolus, transiently blocked peristalsis, but caused maintained block when infused. Hexamethonium blocked propulsive contractions. Inhibition of nitrergic transmission converted regular peristalsis to non-propulsive contractions. These studies demonstrate the utility of an adapted Trendelenburg method for quantitative investigation of motility and pharmacology of enteric reflexes in vivo.     

Manometric responses of human duodenum during infusion of HCl,hyperosmolar saline,bile and oleic acid

Abstract Duodenal motor activity is incompletely understood. The purpose of this study was to define the contractile patterns of the duodenum that occur in response to rate controlled injection of various solutions. In nine healthy volunteers we placed a six channel perfused catheter, and recorded pressure activity in the antrum, pylorus and duodenum. Volumes of 10 and 20 mL of 0.9% NaCl, 100 mM HCl (pH 1), 5% NaCl (1711 mOsm/kg), human bile and iso-osmolar sodium oleate were randomly injected into the duodenum at 20 ml/min, starting IS min after phase III migratory motor complex (MMC). A 20 mL bolus of each solution caused more activity (P < 0.05) than a 10 mL bolus, but the motor pattern was similar. The control, 0.9% NaCl, produced occasional pressure waves, whereas bile and sodium oleate induced more (P < 0.05) activity which consisted of low amplitude, isolated or clusters (2–4 cycle/min) of non-propagating pressure waves that occurred at random sites. In three subjects, oleate produced isolated pyloric phasic contractions. In contrast, HCl and 5% NaCl induced high amplitude pressure waves that were seen either at a single channel or at multiple channels, occurring simultaneously. The motility index was also greater (P < 0.05) than that induced by other solutions. Additionally, within 2 min of infusion, a phase III MMC like pattern was observed in five of the nine subjects who received HCl and three of the nine who received 5% NaCl. A non-nutrient iso-osmolar solution induced occasional motor activity. HCl and hyperosmolar solutions induced more frequent and large amplitude, segmental contractions whereas lipid and bile induced fewer and smaller amplitude contractions. The volume, the pH, the osmolar and the nutrient make up of the infusate may each influence the duodenal motor responses.     

Small intestinal dysmotility following abdominal irradiation in the rat small intestine

Abdominal symptoms such as diarrhoea, abdominal cramps and vomiting are common during and after abdominal radiotherapy for gynaecological and pelvic malignancy. It has recently been recognized that small intestinal dysmotility may contribute to these symptoms but the underlying mechanisms are unclear in part because of the technical difficulties inherent in performing studies in irradiated small intestine. The aim of the current study was to evaluate small intestinal motor activity using perfused micromanometric techniques in 6–8-cm segments of ileum during arterial perfusion with isotonic oxygenated fluorocarbon solution. Intestinal segments from six rats were studied 4 days after treatment with 10 Gy abdominal irradiation. Ileal segments from nine nonirradiated animals acted as controls. For each experiment the total number of pressure waves, high-amplitude (>20 mmHg, long-duration >6 sec) pressure waves, and long (>20 associated) bursts of pressure waves were determined. Irradiation had no effect on the overall number of pressure waves, but increased high-amplitude long-duration (HALD) pressure waves (248 vs 7, P < 0.01). In control animals HALD waves were localized to a single recording site but after radiotherapy 74% of HALD waves were temporally associated with similar pressure waves in other manometric channels. Forty-seven per cent of associated HALD waves migrated aborally. Retrograde migration of HALD waves was seen in five segments following irradiation. Irradiation abolished bursts of >20 pressure waves. High-amplitude contractions which migrate aborally are likely to contribute to diarrhoea after abdominal irradiation. The in vitro small animal model of radiation enteritis will permit interventions to provide further insights into the mediation of intestinal dysmotility.     

Coronary vasodilatation induced by calcitonin gene-related peptide in the anaesthetised pig

The ability of CGRP to increase blood flow in the coronary circulation of the anaesthetized pig was studied in a constant pressure perfusion model. Human alpha-CGRP, when infused close-arterially into the left anterior descending coronary artery perfused at constant pressure, produced a marked and prolonged dose-related increase in coronary flow, at doses above 10 pmol min-1. The gradient of the flow/pressure curves at each dose increased with an increase in pressure, indicating a drop in the resistance of the coronary bed. No significant change was observed in heart rate, left ventricle pressure, mean arterial pressure or cardiac output.     

Anticonvulsant effects of calcium channel blockers in partial and generalized model epilepsies

The calcium channel blockers D890 and verapamil reduced neuronal calcium currents in single snail neurons with intra- and extracellular applications, respectively. Epileptic discharges of single neurons in the rat's motor cortex (in vivo) were depressed in amplitude by intracellular injection of D890. Focal seizure discharges and generalized tonic-clonic seizure activity in the cerebral cortex of the rat were reduced by intracerebroventricular perfusion of verapamil. In non-epileptic rats verapamil failed to exert a depressive effect on somatosensory evoked potentials and on the waves of the spontaneous EEG.     

Effect of nitric oxide on propagated clusters of spontaneous motor waves in an ex vivo rabbit intestinal preparation

The aim of this study was to determine whether nitric oxide can play a role in regulating the propagation of spontaneous motor activity in a rabbit intestinal preparation completely excluded from any central and vascular connection. Experiments were done on nine rabbits of either sex, weighing 2.5 ± 0.5 kg (mean ± SD). After one week of semiliquid diet the animals were sacrificed and a segment including the stomach, duodenum and part of the jejunum was removed and placed into a single chamber organ bath containing 1 L of oxygenated Krebs' solution. Four strain gauges connected to a Dynograph Recorder were sutured on the serosal surface 10 cm apart starting from the gastric antrum to the distal duodenum. Once the motor activity was stabilized, N-nitro-L-arginine methyl-ester (L-NAME) was added to the bath at increasing concentration from 10^?7 to 10^?4. Spontaneous motor activity was recorded, characterized by the cycling occurrence of bursts of waves, starting from the stomach and propagating to the descending duodenum. L-NAME at higher concentrations reduced the time interval between the bursts of waves with a concomitant increase in the propagation velocity of the motor activity. No change in the frequency of waves was detected. The effect of L-NAME was prevented by the administration of L-Arginine. This study suggests an important role for the nitric oxide pathway in the distal propagation of the spontaneous motor activity of the alimentary tract.     

Effect of salbutamol on regional cerebral oxygen consumption, flow and capillary and arteriolar perfusion

This study quantitatively determined the effect of salbutamol (1 microgram kg-1), a beta 2-adrenoceptor agonist, on the perfusion of the brain microvasculature, cerebral O2 consumption, O2 extraction and cerebral blood flow (CBF) in conscious rat. Indices of arteriolar and capillary structure and the percentage of the total cerebral microvascular volume/mm3 (% Vv) and number/mm2 (% Na) perfused were determined. These parameters were obtained from the perfused microvessels, identified by the presence of fluorescein isothiocyanate (FITC) - dextran, and compared with the entire microvascular bed, identified by alkaline phosphatase stain. Cerebral O2 extraction was determined microspectrophotometrically and CBF was determined using 14[C]iodoantipyrine in another group of salbutamol-treated rats. The acute administration of salbutamol did not alter systemic arterial blood pressure. Significant tachycardia was noted in the salbutamol-treated rats. Salbutamol resulted in a significant increase in the percentage of arterioles perfused. Average percentage perfused capillary Na increased significantly from 46 +/- 2 to 88 +/- 1%; %Vv increased significantly and similarly in the arteriolar and capillary beds in all brain regions examined. Average cerebral O2 consumption increased significantly from 3.0 +/- 0.2 to 7.4 +/- 0.7 ml O2 min-1 100 g-1 with salbutamol, while cerebral O2 extraction was unchanged. Average CBF increased from 50 +/- 2 to 142 +/- 9 ml min-1 100 g-1 with salbutamol. Salbutamol may increase the perfusion of the regional microvasculature by increasing cerebral O2 consumption (metabolic vasodilation) and CBF and microvascular perfusion secondarily, although a direct effect of salbutamol on cerebral microvessels cannot be ruled out.     

Effect of endothelin on cortical microvascular perfusion in rats

We used laser-Doppler flowmetry to study the effects of endothelin-1 on local cortical microvascular perfusion and resistance in 29 pentobarbital-anesthetized rats. Intravenous administration of 10-300 pmol endothelin-1 reduced arterial blood pressure and microvascular resistance and increased microvascular perfusion. However, intracarotid administration of low doses of endothelin-1 increased microvascular perfusion and reduced microvascular resistance and arterial blood pressure, whereas high doses (greater than or equal to 300 pmol) reduced microvascular perfusion and increased microvascular resistance and arterial blood pressure. Only the high dose/low flow response was associated with attenuation of the electrocorticogram. The low dose/high flow and high dose/low flow responses to endothelin-1 were not altered by blockade of muscarinic and adrenergic receptors. In addition, systemic metabolic changes (arterial pH, PaCO2, PaO2, and plasma glucose concentration) did not account for the cerebrovascular effects of endothelin-1. Platelet hyperaggregability also did not appear to be a causative factor in the high dose/low flow response to endothelin-1. In fact, ex vivo rat platelet aggregation was inhibited by intracarotid administration of 300 pmol endothelin-1. In conclusion, the cerebral vasculature exhibits extreme sensitivity to the vasodilator properties of endothelin-1 at low doses. The ischemic vasoconstrictor effects observed at high doses implicate endothelin-1 as an important mediator of cerebral vasospasm and/or postischemic hypoperfusion.     

Motor patterns and propulsion in the rat intestine in vivo recorded by spatio-temporal maps

We have used spatio-temporal maps derived from video images to investigate propagated contractions of the rat small intestine in vivo. The abdomen, including an exteriorized segment of jejunum, was housed in a humid chamber with a viewing window. Video records were converted to spatio-temporal maps of jejunal diameter changes. Intraluminal pressure and fluid outflow were measured. Contractions occupied 3.8 +/- 0.2 cm of intestine and propagated anally at 3.1 +/- 0.2 mm s(-1) when baseline pressure was 4 mmHg. Contractions at any one point lasted 8.7 +/- 0.6 s. Contractions often occurred in clusters; within cluster frequencies were 2.28 +/- 0.04 min(-1). Pressure waves, with amplitudes greater than about 9 mmHg, expelled fluid when the baseline pressure was 4 mmHg. In the presence of L-NAME, circular muscle contractions occurred at a high frequency, but they were not propagated. We conclude that video recording methods give good spatio-temporal resolution of intestinal movement when applied in vivo. They reveal neurally-mediated propulsive contractions, similar to those previously recorded from intestinal segments in vitro. The propagated contractions had speeds of propagation that were slower and frequencies of occurrence that were less than speeds and frequencies of slow waves in the rat small intestine.     

Effects of electrical stimulation on intracranial pressure and systemic arterial blood pressure in cats. Part I: Stimulation of brain stem

It has been suggested that brain stem activity is involved in the occurrence of pressure waves. Different sites in the brain stem were activated by electrical stimulation in cats anaesthetized with sodium pentobarbital, to produce an increase in intracranial pressure (ICP) similar to the pressure waves. Then the effect of artificial ventilation on the occurrence of the pressure wave-like response produced under spontaneous respiration was examined since Lundberg's A-waves appear even in artificial ventilation, and B-waves are effaced during artificial ventilation. This results in a brain stem map of ICP and systemic arterial blood pressure (BP) produced by electrical stimulation during spontaneous respiration. Stimulation of the rostral medullary reticular formation produced a rise in ICP and BP in association with a change in the rhythm of the spontaneous respiration; with artificial ventilation, stimulation produced a rise in BP but ICP kept almost at the same level. However, the rise in ICP that was produced by stimulation of the caudal medullary reticular formation during spontaneous respiration also occurred with a depressor response of BP during controlled ventilation. The pressure wave-like responses could be classified, therefore, into two types. One was the response seen during both spontaneous and controlled ventilation, which we designated the 'alpha' wave. The other was the response seen only during spontaneous ventilation, the 'beta' wave. These observations suggest that the origins of A- and B-waves may be related to those of 'alpha' and 'beta' waves, respectively.     

Effect of Intraduodenal Infusion of Acid on the Antropyloroduodenal Motor Unit in Human Volunteers

Intraduodenal acid has been shown to delay gastric emptying. We have investigated the effect of infusing hydrochloric acid into the duodenum on the motor activity of the gastric antrum, pylorus, and duodenum in 18 healthy volunteers. Pressures in the gastric antrum, pylorus, and duodenum and the pH in the antrum and duodenum were recorded in response to alternate duodenal infusions of normal saline and 0.1 M isotonic hydrochloric acid at constant (1 or 2 ml/min) or increasing (1, 2, 3.75, and 5 ml/min) rates. Repetitive infusions of acid (1 or 2 ml/min) were associated with 1) a decrease in antral pressure waves (p < 0.05), 2) a reduction in coordinated pressure waves involving the duodenum (p < 0.05) and replacement by random contractile activity, and 3) an increase in isolated pyloric pressure waves (IPPWs) (p < 0.05). Increasing the rate of acid infusion reduced the rate of coordinated contractions involving the antrum (r = -0.39; p < 0.01) and increased the rate of IPPWs (r = 0.45; p < 0.01). There were significant correlations between the percentage of time that the duodenal pH was less than 2, and both the rate of coordinated contractions involving the antrum (r = -0.28; p < 0.01) and the rate of IPPWs (r = 0.34; p < 0.01). These changes in antropyloroduodenal motor activity may contribute to the delay in emptying of acidic solutions from the stomach.     

Further data on the inhibitory enterogastric reflex triggered by intestinal osmotic changes in cats

The relationship between osmotic pressure in the intestinal lumen and gastric motor activity was studied in anesthetized cats. For this purpose the EMG was recorded in the antrum while the small intestine (duodenum and the first part of jejunum) was perfused with various solutions: tap water (5 mOsm), NaCl, mannitol and glucose having an osmotic pressure of 70, 138, 275, 550 or 1100 mOsm. Hypotonic and hypertonic solutions both induced a decrease in the gastric activity, i.e. an increase in period of electrical control activity. This effect was found to depend both on the osmolarity value (the osmotic pressures furthest removed from the isotonic value produced the greatest effect) and on the substance used (glucose, mannitol and NaCl, in decreasing order of efficiency). The isotonic solution of glucose and, to a lesser extent, of mannitol was also active, unlike the isotonic solution of NaCl. All these gastric changes were prevented by cervical bivagotomy. It was concluded that the vagal osmosensitive receptors located in the small intestine trigger this inhibitory enterogastric reflex which probably constitutes an important part in the regulation of gastric emptying.     

In vitro motor activity of intestinal segments of streptozotocin diabetic rats

The spontaneous motor activity of the isolated segments of the gut of streptozotocin-diabetic rats was studied in vitro. In normal preparations, the frequency of intraluminal pressure changes was little influenced by raising the intraluminal pressure. In contrast, in diabetic preparations, the frequency tended to increase with a rise of the intraluminal pressure, and the pressure waves were more irregular than in controls. The motor frequency with a pressure load of 3 cm H2O in the duodenum was 33/min in control rats and 21/min in diabetic rats. The motor frequencies in the other intestinal segments were also higher in normal preparations than in diabetic ones, although these differences were statistically not significant. The amplitude of intraluminal pressure changes increased according to the increase of pressure load, both in normal and diabetic preparations. These amplitudes were higher in normal than in diabetic preparations; however, the differences were statistically significant only in the jejunum. Insulin treatment (5 U/day) for one month, one to two months after streptozotocin injection, lowered the plasma glucose level to nearly normal and increased the body weight up to 80% of the normal but did not re-establish the normal motor frequency in the duodenum. Moreover, treatment of diabetic rats with aldose reductase inhibitor, ONO-2235 (per os, 50 mg/kg b.w./day for one month, one to two months after streptozotocin injection) did not re-establish the normal rhythms in duodenum. The pacemaker activity as well as mechanical properties in the intestinal tract may be disturbed in diabetic preparations.     

Effects of absorption rate,flow rate and fluid load on colonic motor activity in dogs

Abstract We investigated the relationship between absorption rate, flow rate, fluid load and colonic motor activity in an in vivo isolated colonic loop model. Motor activity was recorded by implanted strain gauge transducers. Two electrolyte solutions were perfused at 0.4 and 1.6 mL min^?1 through the open colonic loop (distal end open) or infused into the closed loop (distal end closed). The first solution resembled ileostomy fluid (ES1) and the second solution was an iso-osmolar mannitol solution (ES2). The absorption rate for H₂O measured by ¹⁴C PEG concentrations of ES2, 0.2 ± 0.03 mL min^?1, was significantly less than that of ESI, 0.6 ± 0.06 mL min^?1. Infusion of ES1 under open loop conditions served as control. Motor activity was analysed for area under contractions and expressed as motor index ratio in comparison to the control. None of the solutions altered motor activity when perfused at the two rates through the open loop. Under closed loop conditions, the infusion of either solution at 0.4 mL min^?1 had no significant effect on colonic motor activity. Infusion of ES1 or ES2 at 1.6 mL min^?1 into the closed loop, however, increased the motor index ratio 2.5-fold and 3.6-fold, respectively (P < 0.01). The proximal half of the colon was less affected than the distal half during infusion of ES1 but not during infusion of ES2. We conclude that flow rate and absorption rate do not influence colonic motor activity as long as the fluids can leave the colon. When the distal end is closed, inflow, resulting in fluid accumulation and distension, leads to stimulation of colonic motor activity.     

Effects of electrical stimulation on intracranial pressure and systemic arterial blood pressure in cats: Part I: Stimulation of brain stem

It has been suggested that brain stem activity is involved in the occurrence of pressure waves. Different sites in the brain stem were activated by electrical stimulation in cats anaesthetized with sodium pentobarbital, to produce an increase in intracranial pressure (ICP) similar to the pressure waves. Then the effect of artificial ventilation on the occurrence of the pressure wave-like response produced under spontaneous respiration was examined since Lundberg’s A-waves appear even in artificial ventilation, and B-waves are effaced during artificial ventilation. This results in a brain stem map of ICP and systemic arterial blood pressure (BP) produced by electrical stimulation during spontaneous respiration. Stimulation of the rostral medullary reticular formation produced a rise in ICP and BP in association with a change in the rhythm of the spontaneous respiration; with artificial ventilation, stimulation produced a rise in BP but ICP kept almost at the same level. However, the rise in ICP that was produced by stimulation of the caudal medullary reticular formation during spontaneous respiration also occurred with a depressor response of BP during controlled ventilation. The pressure wave-like responses could be classified, therefore, into two types. One was the response seen during both spontaneous and controlled ventilation, which we designated the ‘α’ wave. The other was the response seen only during spontaneous ventilation, the ‘β’ wave. These observations suggest that the origins of A- and B-waves may be related to those of ‘α’ and ‘β’ waves, respectively.     

Effects of modulators of Ca2+-activated, intermediate-conductance potassium channels on motility of the rat small intestine, in vivo

The movements of the intestine shift between different motor patterns, including between propulsion and mixing, but there is little information concerning mechanisms that may lead to changes in the patterns of motility. We have investigated the influence on intestinal motility of drugs that affect the after-hyperpolarization potential (AHP) of intrinsic primary afferent neurons (IPANs). The current of the AHP is carried by the intermediate conductance, calcium-activated, potassium (IK) channel. In anaesthetized rats, the IK channel blocker, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (0.05-1 mg kg(-1), i.v.) disrupted the regular propulsive pressure waves that occur in the small intestine and reduced propulsion of the contents (after 1 mg kg(-1), the fluid propelled was <25% of control). If the propulsion in the intestine was regular, the IK channel opener, 5,6-dichloro-1-ethyl-2-benzimidazolinone (DC-EBIO, 0.1 mg kg(-1) h(-1)) had no effect. DC-EBIO (0.1 mg kg(-1) h(-1)) restored propulsive activity after the nitric oxide synthase inhibitor, Nomega-nitro-l-arginine had changed motility to a mixing pattern. We suggest that the AHP determines the synchrony of action potential firing in synaptically coupled IPANs, and that this synchrony influences the patterns of firing of muscle motor neurons, and hence the pattern of contraction of the muscle and whether the pattern is predominantly propulsive or predominantly mixing.     

Modulation of cardiovascular and electrocortical activity through serotonergic mechanisms in the nucleus tractus solitarius of the rat

The nucleus tractus solitarius (NTS) is an integral part of the baroreceptor reflex arc. Thus, stimulation of the NTS elicits changes in arterial pressure and heart rate as well as in numerous other physiologic parameters including electrocortical activity. Serotonin (5-HT), which has been implicated in cardiovascular and electrocortical control, is present in nerve terminals within the NTS. Therefore, this study was designed to determine whether 5-HT may effect that control within the NTS. Serotonin injected into the NTS of anesthetized rats produced marked changes in the EEG, arterial pressure, and heart rate. EEG activity changed from irregular 1-5 Hz, 350-500 microV waves with an overlying 13-15 Hz, low voltage rhythm to a regular, 5 Hz, 250-300 microV rhythm. The dose-dependent cardiovascular changes were maximal at a dose of 400 pmol which produced a fall of mean arterial pressure of 48 +/- 2 mm Hg from a baseline of 96 +/- 4 mm Hg and of heart rate of 90 +/- 9 bpm from a baseline of 400 +/- 18 bpm (n = 6; P less than 0.001). Both the cardiovascular and EEG effects of 5-HT injected into the NTS were blocked by the prior injection of the 5-HT antagonist metergoline at the same site. However, the bilateral microinjection of metergoline into the NTS did not affect the baroreceptor reflex. Thus, although serotonergic mechanisms in the NTS may be involved in the modulation of electrocortical and cardiovascular activity, they are not integral to the baroreceptor reflex arc.     

Effects of calcium entry blocker emopamil on postischemic energy metabolism of the isolated perfused rat brain

The effects of emopamil on postischemic energy metabolism and electroencephalographic (EEG) recovery were investigated in the isolated rat brain perfused at either constant pressure or, alternatively, at constant flow rate. Flow rate and perfusion pressure were monitored continuously. The brains were perfused with a fluorocarbon emulsion for 30 min, and after 30 min of ischemia, perfusion was reinstituted for 5, 30, or 60 min. Global cerebral perfusion rate was increased by emopamil throughout the perfusion period and, accordingly, in brains perfused at a constant flow rate, perfusion pressure was reduced by the drug. At constant pressure perfusion, after 5 min after ischemia, cortical levels of creatine-phosphate, adenosine triphosphate (ATR), glucose, glucose-6-phosphate, and fructose-6-phosphate were higher in emopamil-treated brains than in controls, although the levels of adenosine diphosphate (ADP) and adenosine monophosphate (AMP) were reduced. When brains were perfused at constant flow rate, however, emopamil exhibited no effect on brain energy metabolism in the early reperfusion period. Postischemic restoration of high-energy phosphates proved to depend on the flow rate used. After 30 min of postischemic reperfusion, cortical levels of lactate were lower in emopamil-treated brains compared to controls at both constant pressure and constant volume perfusion. Postischemic lactate levels were independent of flow rate and were also reduced when emopamil was only present during reperfusion. The postischemic restoration of cortical EEG activity was improved by the calcium entry blocker.(ABSTRACT TRUNCATED AT 250 WORDS)