Effect of intravenous infusion of proglumide on ruminal motility in conscious sheep (<Emphasis Type="Italic">Ovis aries</Emphasis>)

The effects of intravenous infusion of proglumide on regular ruminal contractions were examined in conscious sheep using doses that inhibit pancreatic exocrine secretion. After a control period of 20 min, proglumide was infused intravenously for 40 min at a dose of 15, 30 or 60 μmol/kg per min and venous blood was collected. The intravenous infusion of proglumide significantly increased the frequency of ruminal contractions at 15 μmol/kg per min without altering the amplitude, while it significantly decreased the frequency and amplitude of ruminal contractions at 30 and 60 μmol/kg per min in a dose-dependent manner. Proglumide did not increase contractile activity of the omasum, abomasum and duodenum or the plasma concentration of immunoreactive cholecystokinin (CCK). Application of proglumide at 1–30 mmol/L inhibited bethanechol-induced contraction in both longitudinal and circular muscle strips of the dorsal sac of the rumen. These results suggest that proglumide at a low dose acts indirectly on the rumen as a CCK receptor antagonist to increase the frequency of contractions, whereas at higher doses it inhibits cholinergic-induced contraction of the ruminal muscles or acts as an agonist to inhibit contractions in sheep. Hence, proglumide at high doses seems unsuitable for research or therapeutic use as a CCK receptor blockade in sheep.     

Inhibition of endogenous nitric oxide production influences ovine hindlimb metabolism independently of insulin concentrations

The hindlimb arteriovenous difference (AVD) model was used to determine whether 30 mg/ kg of the nitric oxide synthase (NOS) inhibitor L-NGnitroarginine methyl ester (hydrochloride; L-NAME) inhibited ovine NO synthesis and influenced muscle metabolism. Eight Border Leicester x Merino cross lambs (50 to 55 kg BW) were infused with saline (control) or saline containing L-NAME via an indwelling jugular vein catheter in a balanced randomized crossover design with 3 d between treatments. The abdominal aorta and deep femoral vein were catheterized for assessment of AVD of hind limb metabolism. Arterial hematocrit and insulin concentration and both arterial and venous concentrations of nitrate/nitrite (NOx), glucose, lactate, NEFA, and urea were determined. Infusion of L-NAME decreased arterial NOx concentrations (P = 0.049), indicating inhibition of systemic NO synthesis. Treatment had no effect on arterial (3.5 vs. 3.6 +/- 0.19 mmol/L for control and L-NAME lambs, respectively; P = 0.39) or venous (3.3 vs. 3.4 +/- 0.16 mmol/L, P = 0.55) plasma glucose concentrations or on glucose AVD (0.19 vs. 0.27 +/- 0.065 mmol/L, P = 0.20). There was an interaction (P = 0.038) between time and treatment, such that L-NAME initially increased the AVD of glucose (up to 180 m) divergent from control lambs. The response was then decreased before a possible inflection beyond 240 min. Infusion of L-NAME increased hindlimb venous NEFA (222 vs. 272 +/- 13.2 micromol/L, P = 0.007) and NEFA AVD (79.4 vs. -13.3 +/- 31.5 micromol/L, P = 0.018). These metabolic changes were independent of plasma insulin concentrations, which were not affected by L-NAME infusion (25.3 vs. 27.8 +/- 3.62 mU/L, P = 0.85). The increase in hindlimb lipolysis after L-NAME infusion does not seem to be due to increased lipolysis of plasma triacylglycerol because circulating arterial (155 vs. 142 +/- 20.8 micromol/L, P = 0.58), venous (154 vs. 140 +/- 20.5 micromol/L, P = 0.50), and AVD (1.0 vs. 2.9 +/- 3.17 micromol/L, P = 0.38) triacylglycerol concentrations were unaffected by L-NAME infusion. In conclusion, these data indicate that infusion of 30 mg of L-NAME/kg inhibits NO synthesis, which in turn influences fat and carbohydrate metabolism in the ovine hindlimb independently of plasma insulin concentrations.     

Role of nitrergic nerves in the regulation of motility of the omasum and abomasum in healthy sheep <Emphasis Type="Italic">(Ovis aries)</Emphasis>

We examined the physiological role of nitrergic nerves in the regulation of omasal and abomasal motility in conscious healthy sheep and omasal muscle specimens. Nitric oxide (NO)-donor, S-nitroso-acethyl-dl-penicillamine (SNAP, 3-30 nmol/kg per min, i.v.) significantly inhibited omasal electromyographic (EMG) activity, whereas it did not alter EMG activity in the abomasal antrum. However, NO synthase inhibitor, Nomega-nitro-l-arginine-methyl ester (L-NAME, 0.3-3.0 micromol/kg per min, i.v.) did not alter EMG activity of the omasum and abomasum. In the in vitro experiments, SNAP application (6-200 micromol/l) significantly inhibited bethanechol (10 micromol/l)-induced contraction of longitudinal and circular muscles of the omasum. L-NAME application (0.03-3.0 mmol/l) enhanced electric field stimulation-induced contractions of the circular muscles. The results suggest that the omasal muscles are responsive to exogenous NO and that nitrergic nerves innervate the circular muscle layer of the omasum, however, nitrergic nerves are not or scarcely involved the physiological regulation of omasal and possibly abomasal motility in healthy sheep.     

Loperamide: evidence for a centrally mediated opioid effect on rumen motility in conscious goats and sheep

Loperamide inhibited the frequency and amplitude of cyclical contractions of the rumen in conscious goats (100 micrograms/kg, i.v. and sheep (250 micrograms/kg, i.v.). In goats, the inhibitory effect of loperamide could be prevented by pretreatment with the opiate antagonist naltrexone (greater than or equal to 12.5 micrograms/kg, i.v.) but not by pretreatment with the dopaminergic antagonist domperidone (500 micrograms/kg, i.v.). Intracerebroventricular administration of 1 microgram/kg loperamide in goats significantly depressed ruminal contraction frequency, whereas intravenous administration of 10 micrograms/kg loperamide did not affect cyclical motility. Administered via the carotid artery, loperamide (4 micrograms/kg) depressed both frequency and amplitude of cyclical contractions of reticulum and rumen, whereas the same dose was ineffective via the coeliac artery. In vitro, loperamide (10 nM-100 microM) had no influence on spontaneous activity or tone of the reticular longitudinal muscle strips. It is concluded that loperamide inhibits cyclical ruminal contractions through a central opioid pathway.     

Central and local actions of opioids upon reticulo-ruminal motility in sheep

The effects of opioids and naloxone on cyclical forestomach motility were determined in anaesthetized and conscious sheep. To assess central or peripheral opioid actions, differential routes of administration were used. Possible dynamic effects along the innervating vagovagal reflex arc were investigated electrophysiologically at the cervical level of the vagus nerve. Further, direct influences on the smooth muscle were evaluated in vitro on isolated longitudinal reticular strips. Additionally, the effects of some spasmogenic agents were studied for comparative purposes. In anaesthetized sheep, opioids depressed in an identical manner both the amplitude of spontaneous cyclical contractions and contractions evoked by electrical stimulation of the distal end of the cut cervical vagus. In conscious sheep, low doses of normorphine and loperamide inhibited frequency and amplitude centrally (20 micrograms/kg and 4 micrograms/kg via carotid artery respectively), whereas locally higher dose levels (200 micrograms/kg and 10 micrograms/kg via coeliac artery respectively) affected only the amplitude of cyclical contractions. Furthermore the opioid peptides Leu-, Met-enkephalin and [D-Ala2-Met5]-enkephalinamide preferentially depressed the amplitude of cyclical motility most efficiently if administrated via the coeliac artery. These results indicate the presence both of a central opioid action depressing frequency and amplitude and of a local opioid action depressing only the amplitude of cyclical reticulo-ruminal motility. Opioids did not alter the resting discharge of afferent tension units and similarly failed to modulate tone of reticular strips in vitro, suggesting that the opioids act locally on the intramural neuronal plexus, possibly by diminishing the output of excitatory transmitter. Whether substance P could play a role as a vagal excitatory transmitter besides the classically implicated acetylcholine has been discussed. The central opioid mechanism is probably not situated within the gastric centres but elsewhere in the brain. Naloxone (greater than or equal to 100 micrograms/kg, jugular vein) stimulated the frequency of cyclical ruminal motility only in well-defined experimental conditions, probably via a central mechanism.     

The effect of intravenous insulin infusion on renal blood flow in conscious sheep is partially mediated by nitric oxide but not by prostaglandins

To test the effect of insulin on renal perfusion and the participation of NO and PG as mediators of this response, renal blood flow (RBF) was measured in sheep (n = 8) implanted with ultrasonic flow probes around renal arteries and with a systemic arterial pressure (SAP, n = 4) telemetry device. Three protocols were performed: 1) RBF and SAP were recorded (0800 to 1800 h) in fed and fasted sheep, with the latter receiving intravenous (i.v.) infusions (0.5 mL/min) of insulin at 2 or 6 mU/(kg·min); 2) fasted sheep received i.v. infusions of either an inhibitor of NO synthesis (N(G)-nitro-L-arginine methyl ester, L-NAME) alone [0.22 mg/(kg·min), 1000 to 1200 h] or L-NAME (1000 to 1200 h) + insulin during the second hour (6 mU/(kg·min), 1100 to 1200 h); and 3) the same protocol was followed as in protocol 2, substituting L-NAME with ketoprofen [0.2 mg/(kg·min)], a cyclooxygenase inhibitor. In all protocols, plasma insulin and glucose were determined. During insulin administration, euglycemia was maintained and hypokalemia was prevented by infusing glucose and KCl solutions. After the onset of meals, a long-lasting 18% increase in RBF and a 48% insulin increase were observed (P < 0.05), without changes in SAP. Low- and high-dose insulin infusions increased RBF by 19 and 40%, respectively (P < 0.05). As after meals, the increases in RBF lasted longer than the insulin increase (P < 0.05). The L-NAME infusion decreased RBF by 15% (P < 0.05); when insulin was added, RBF increased to preinfusion values. Ketoprofen decreased RBF by 9% (P < 0.05); when insulin was added, RBF increased to 13% above preinfusion values (P < 0.05). In no case was a modification in SAP or glucose noted during the RBF changes. In conclusion, insulin infusion mimics the meal-dependent increase in RBF, independent of SAP, and lasts longer than the blood insulin plateau. The RBF increase induced by insulin was only partially prevented by L-NAME. Ketoprofen failed to prevent the insulin-dependent RBF increase. Both facts suggested that complementary vasodilatatory agents accounted for the insulin effect on sheep renal hemodynamics.     

Alleviation of excessive gas accumulation in the ruminant stomach by ritanserin

The relationships between forestomach motility and eructation rate were studied in sheep and cattle. Three ewes and 2 heifers were implanted with strain gauges on the reticulo-rumen and fitted with a cannula in the dorsal sac of the rumen. Studies were performed in sheep after induction of hypocalcemia by Na2EDTA infusion and cattle were studied after ruminal distension. Experiments were performed by measuring the rate and volume of eructated ruminal gases, using a technique by which the trachea is transected. The frequency of reticulo-ruminal contractions decreased 40% within 30 minutes of Na2EDTA infusion to the sheep. The volume of eructated gas (for 30-minute periods) decreased from 10.7 L to 5.5 L at the end of the 60-minute infusion period. Pretreatment with ritanserin (0.1 mg/kg, subcutaneously) not only prevented bloating during the ruminal stasis induced by hypocalcemia, but also significantly increased the eructated volume of gas. In cattle, ritanserin given at the same dose level (0.1 mg/kg, subcutaneously) significantly increased the volume of eructated gas after ruminal distension. This study supports the hypothesis that the caudal esophageal sphincter has a role in the rate of ruminal gas eructation and indicates that its relaxation may be due to a 5-hydroxytryptamine antagonist.     

Involvement of neuronal nitric oxide synthase (nNOS) in the regulation of migrating motor complex (MMC) in sheep

The objectives of this study were to evaluate the role of nitric oxide (NO) synthase isoforms (nNOS, eNOS, and iNOS) in the regulation of the migrating motor complex (MMC) in sheep using electromyography and their expression in the gastrointestinal (GI) tract by Western blot (WB) and immunohistochemistry. Intravenous administration of L-NAME or the nNOS inhibitor 7-nitroindazole (7-NI) decreased the MMC interval. Myoelectric activity of intestinal phase II was increased, whereas antral activity was reduced. These effects were blocked by L-arginine. Inhibitors of either iNOS (aminoguanidine and S-methylisothiourea) or eNOS (L-NIO) were ineffective. The NO donor sodium nitroprusside decreased GI myoelectric activity, inhibited the MMC pattern, and prevented the effects induced by L-NAME and 7-NI in the intestine. Intracerebroventricular administration of these agents did not modify GI motility. In the rumen, abomasal antrum, duodenum, and jejunum, WB showed three bands at about 155, 145, and 135kDa corresponding to nNOS, and a 140-kDa band (eNOS); however iNOS was not detected. Positive nNOS immunostaining was observed in neurons of the myenteric and submucous plexus of all GI tissues, while eNOS was found in the endothelial cells, ruminal and intestinal epithelium, as well as in some enteric neurons and in endocrine-like cells of the duodenal Brunner's glands. In contrast, only weak iNOS immunoreactivity was found in ruminal epithelium. Taken together, our results suggest that NO, synthesized at a peripheral level by nNOS, is tonically inhibiting the MMC pattern and intestinal motility in sheep.     

Luteotrophic and luteolytic effects of nitric oxide in sheep are dose-dependent in vivo

It has been suggested that nitric oxide (NO) acts in either an anti-luteolytic or in a luteolytic manner, but the mechanism for these opposing roles is unclear. We hypothesized that NO may act in a dose-dependent manner to regulate luteal function, whereby low concentrations of NO might stimulate luteal progesterone production (i.e. luteotrophic) and high concentrations of NO might reduce concentrations of plasma progesterone (i.e. luteolytic). To test this hypothesis we infused increasing concentrations of the fast-acting NO donor, dipropylenetriamine NONOate (DPTA), into the arterial supply of sheep with ovarian transplants bearing a corpus luteum (CL). Infusions were performed on sheep with CL 11 days of age (n=9) or over 30 days of age (n=15). We measured changes in the concentration of progesterone in ovarian venous plasma during the 1-h infusion and for 24h after the infusion, and then compared the mean concentration of progesterone between treatment groups for effects by dose and dose by period interactions. Compared with saline-treated controls (n=6), the highest dose of 1000 microg/min DPTA (n=6) reduced (P0.05) in sheep infused with the lowest dose of 1 microg/min DPTA (n=6) compared with controls. We conclude that NO regulates luteal function in a dose-dependent manner in sheep in vivo.     

Localization of CCK-1R in the omasum and role of CCK in the regulation of omasal contractions in sheep

The present study examined localization of cholecystokinin receptor (CCK-R) mRNA in the muscle layer of the ovine omasum and role of CCK-R type 1 (CCK-1R) in the regulation of muscle contraction of the omasum. We demonstrated that not only CCK-R type 2 (CCK-2R) mRNA but also CCK-1R mRNA is highly expressed in the muscle layer of the ovine omasum. Application of CCK-8 to muscle strips of the greater curvature of the ovine omasum at 1-100 nM induced tonic contraction in a concentration-dependent manner, and the contractile effect of CCK-8 was inhibited by both CCK-1R antagonist lorglumide (IC(50) 2.7 and 7.9 microM in the longitudinal and circular muscle, respectively) and CCK-2R antagonist PD135,158 (IC(50) 51.4 microM in the longitudinal muscle), indicating that not only CCK-2R but also CCK-1R is functionally expressed in the plasma membrane of smooth muscles in the omasum and mediates action of exogenous CCK. Contractile effect of intravenous infusion of CCK-8 (1-30 pmol/kg/min) on omasal contraction was also confirmed in the in vivo experiments using conscious sheep in the absence and presence of atropine infusion (14.4 nmol/kg/min), and showed that circulating CCK increases omasal electromyographic (EMG) activity at lower plasma concentration than that it inhibits ruminal contractions. Taking account of our previous results in the in vivo study using other CCK-1R antagonist, it is suggested that circulating CCK, even at normal range of plasma concentration, plays a physiological role as a regulator of omasal contractions in sheep and CCK-1R mediates the action of CCK.     

Pulmonary arterial pressure and electrocardiograms in broiler chickens infused intravenously with L-NAME,an inhibitor of nitric oxide synthase,or sodium nitroprusside (SNP), a nitric oxide donor

1. Broilers were divided at 42 to 44 d of age into a Control group (n=30) and a Treatment group (n=30). The mean pulmonary arterial pressure (mPAP) and electrocardiogram (ECG) leads II and aV(F) were measured 1, 2 and 4 h after an intravenous injection of 0.9% saline (Control group) or Nomega-nitro-L-arginine methyl esther (L-NAME), an inhibitor of nitric oxide synthase and thus an inhibitor of endothelial nitric oxide (NO) production (Treatment group). 2. At 1 and 2 h but not 4 h post-injection, L-NAME significantly increased the mPAP and the amplitudes of the ECG S-wave and RS-wave leads II and aVF when compared with Control values. 3. The correlation coefficients between the mPAP and the ECG S-wave and RS-wave amplitudes for lead II within the Treatment group were -0.848 and -0.553 at 1 h and -0.798 and -0.512 at 2 h, respectively. The corresponding coefficients for lead aVF were -0.735, -0.596, -0.663 and -0.724, respectively. 4. After suitable mPAP and ECG values had been recorded at each time interval, sodium nitroprusside (SNP), which acts as a short-lived NO donor molecule, was injected intravenously via a right-cardiac catheter. Within 5 min after the SNP injection, the mPAP and the ECG lead II S-wave and RS-wave amplitudes were transiently reduced to levels that, at 1 and 2 h after L-NAME injection, did not differ from Control values. Within 10 min after the SNP injection, all values returned to the levels previously induced by L-NAME. 5. These results demonstrate that L-NAME increased the myocardial contractility and PAP, whereas SNP transiently reversed the effects of L-NAME on myocardial contractility and PAP. It appears likely from these results that the pulmonary vascular endothelium releases NO that in turn reduces the pulmonary vascular resistance or attenuates myocardial contractility in broiler chickens.     

Inhibitory action of intravenously administered ammonium acetate on the motility of the rumen in sheep

Summary

The effect of 60 minutes’ intravenous infusions, before morning feeding, of ammonium acetate (18.6 micromole/min/kg of body weight) and ammonium acetate with propranolol (11 μg/min/kg of body weight) on the ruminal motility of sheep was examined. Ammonia has an adrenaline‐like action therefore propranolol, a beta‐receptor blocking agent, was administered in order to eliminate the possible effect of adrenaline on ruminal motility. The contractions of the dorsal sack of the rumen were registered by means of the balloon method, with the gauge inserted through the rumen fistula. The infusion of ammonium acetate caused an increase of the ammonia concentration in the blood to 0.6 mmolel/at the end of 60 minutes’ infusion. Already during the first 5 minutes of the intravenous infusion of ammonium acetate there was a decreased frequency of ruminal contractions, which was observed throughout the infusion. After the infusion there was a radical decrease of the concentration of ammonia in the blood, and at the same time an increase in the frequency of rumen contraction was observed.

Blocking of the beta‐adrenergic receptors by propranolol did not eliminate the inhibiting action of ammonium ion on rumen motility. The infusion of the ammonium acetate caused an increase of adrenaline and glucose concentration. This response was eliminated by propranolol in the case of adrenaline but not glucose. It is assumed that the action of ammonium ion on the rumen motility is derived primarily by the central nervous system.     

Modification by 6-hydroxydopamine (6-OHDA) of the inhibition of extrinsic rumen contractions in sheep produced by beta-endorphin

In sheep, beta-endorphin (1 and 2 micrograms/kg) administered into the third cerebral ventricle caused a significant inhibition of the frequency of rumen contractions. The amplitude of the first rumen contractions, following immediately after the end of infusion, and the average amplitude of primary rumen contractions, were inhibited. Beta-endorphin caused general psychomotor excitability. These results suggest that an inhibitory mu and delta opioid system is involved in the control of forestomach motility and general behaviour in sheep. All effects of beta-endorphin were completely prevented by i.c.v. 6-hydroxydopamine (6-OHDA, 18.2 micrograms/kg) pre-treatment. These results suggest that beta-endorphin-induced inhibition of rumen motility is due to central noradrenergic system activation. The exact location of this noradrenergic system remains to be determined.     

Depression of reticulo-ruminal motor functions through the stimulation of 012-adrenoceptors

Inhibition of the cyclical contractions of the reticulum and the rumen by detomidine (10-40 micrograms/kg, i.v.), xylazine (20-80 micrograms/kg, i.v.) and clonidine (2.5-10 micrograms/kg, i.v.) were compared in sheep and cattle housed individually in box stalls. Two alpha 2-adrenergic receptor blocking agents, tolazoline and yohimbine, were administered intravenously for prevention (0.1-0.4 mg/kg) or reversal (0.4-1.2 mg/kg) of these effects. Continuous recording of the reticuloruminal contractions and measurement of the volume of ruminal gas eliminated through the upper respiratory tract indicated that the three alpha 2-agonists inhibited the primary ruminal contractions associated with the reticular contractions. The occurrence of secondary ruminal contractions was also blocked in sheep, but only suppressed in cattle. The inhibition of reticulo-ruminal contractions was prevented or reversed competitively by the two alpha 2-blocking agents, suggesting an alpha 2-adrenoceptor mediation of the inhibition of cyclical motor activity of the reticulo-rumen. In contrast with tolazoline, yohimbine was unable to alleviate the accumulation of gas resulting from inhibition of the secondary ruminal contractions.     

Effects of ruminal infusion of volatile fatty acids on plasma concentration of growth hormone and insulin in sheep.

In an initial experiment we observed postprandial changes in plasma concentrations of growth hormone (GH), insulin, glucagon, and somatostatin (SRIF) in sheep. We then examined whether increasing the rumen concentration of volatile fatty acids (VFA) by infusing a VFA mixture at three rates (53.5, 107, and 214 micromol/kg/min for 4 hr) mimicked the postprandial changes in hormone secretion. Feeding significantly (P < 0.05) suppressed the plasma GH concentration for 6 hr, whereas it significantly (P < 0.05) increased plasma concentrations of insulin, glucagon, and SRIF. Plasma glucose levels tended to decrease after feeding but then gradually increased over the prefeeding level (P < 0.05). Intraruminal infusion of the VFA mixture at 107 micromol/kg/min caused similar changes in ruminal VFA concentrations to those seen after feeding. The infusion significantly (P < 0.05) suppressed GH secretion in a dose-dependent manner, whereas it caused a significant (P < 0.05) increase in insulin and glucose concentrations without changing glucagon concentrations. From these results, we conclude that the postprandial change in ruminal VFA concentration may be a physiological signal which modifies GH and insulin secretion in sheep.     

Beta-endorphin-induced inhibition of rumen contractions in sheep. The effect of hypothalamic de-efferentiation

In conscious sheep, beta-endorphin (1 and 2 micrograms/kg) administered into the third cerebral ventricle caused psychomotor excitability and a significant inhibition of the frequency of rumen contractions. The amplitude of the first rumen contractions, following immediately after the end of endorphin infusion, and the average amplitude of primary rumen contractions were also inhibited. De-efferentiation at the level of the hypothalamus prevented both the inhibitory effect of beta-endorphin on the frequency of rumen contractions and the drug-induced psychomotor excitability. However, de-efferentiation did not prevent beta-endorphin-induced inhibition of the mean amplitude of rumen contractions. The character of pathohistological changes induced by de-efferentiation showed descending degenerative changes of the nerve tracts connecting the hypothalamus with the pons and the medulla oblongata. These results, together with previously published evidence, do suggest that de-efferentiation at the level of the hypothalamus causes degeneration of inhibitory descending opioid-noradrenergic pathways connecting the hypothalamus with the gastric centres in the medulla oblongata.     

Hypothalamus involvement in the reticulo-rumen motor and behavioural disturbances induced by morphine in sheep

Morphine (20 and 40 µg/kg) administered into the cerebral ventricle of conscious sheep caused significant inhibition of the mean frequency and the average amplitude of primary ruminal contractions by 45 min after injection. Between 90 and 120 min, morphine (40 µg) provoked a significant increase in the amplitude (p<0.01). At both doses it caused strong psychomotor excitability that lasted for more than 140 min. Isolation of the hypothalamus prevented both the inhibitory effects of morphine on rumen motility and the drug-induced psychomotor excitability. Histopathological analysis of slices of the hypothalamus, pons and medulla indicated descending degenerative changes in the nervous pathways connecting the hypothalamus with lower structures in the brain. These results suggest either that hypothalamic isolation caused degeneration of inhibitory descending pathways that connect the hypothalamus with the gastric centres or that structures of importance for forestomach motility are not located within the gastric centres but elsewhere in the brain, for example in the hypothalamus.Abbreviations Ach acetylcholine - CSF cerebrospinal fluid - ICV intracerebroventricular(ly) - NA noradrenalin - 6-OHDA 6-hydroxydopamine - PAGM periaqueductal grey matter     

The effect of central sympathectomy by 6-hydroxydopamine (6-OHDA) on the response to morphine in conscious sheep

When morphine, an opioid -agonist, was administeredin vivo into the third cerebral ventricle (ICV) of conscious sheep at 20 and 40 µg/kg body weight, it caused psychomotor excitability for 2–3 h and a significant decrease in the reticuloruminal frequency for 45 min and in the mean amplitude of the primary contractions for 65 min. From 60 min after infusion, the same doses of morphine caused a significant increase in the average amplitude of the contractions for 45 min. This suggests that an inhibitory -opioid acceptor is involved in the central control of forestomach motility and general behaviour in sheep. All the effects of morphine were completely prevented by pretreatment with 18.2 µg/kg body weight 6-OHDA ICV. These results suggest that both morphine-induced inhibition of rumen motility and psychomotor excitability are due to central noradrenergic descending system activation. The exact location of the noradrenergic system remains to be determined.     

Gastro-intestinal motor disturbances induced by lysine-acetylsalicylate treatment in sheep

The effects of intravenous (i.v.), intramuscular (i.m.) and oral administration of lysine-acetylsalicylate (Lys-ASA) on gastro-intestinal motility were investigated in sheep using electromyography. A dose of 20 mg/kg Lys-ASA intravenously reduced the frequency of reticular contractions for 86 ± 18 min, produced abomasal hypomotility and caused a disruption of the cyclical pattern of intestinal motility for at least 120 min. The frequency of reticular contractions measured from 20 to 30 min after Lys-ASA administration was negatively correlated (ß= 0.97; PΔ0.01) to the log of the dose used for doses varying from 10 to 40 mg/kg. Similar effects were observed with intramuscular and oral dose rates of 40 and 80 mg/kg, respectively. Previous i.v. administration of phentolamine (0.1 mg/kg) or tolazoline (2 mg/kg) abolished the effects of Lys-ASA (20 mg/kg) administered intravenously on both reticular contractions and abomaso-intestinal motility.
It was concluded that Lys-ASA administered at therapeutic doses in sheep produced gastro-intestinal motor disturbances and that α-and α₂-adrenergic antagonists are able to block them.     

Central and peripheral serotonergic control of forestomach motility in sheep

Participation of tryptaminergic receptors in the control of forestomach motility was investigated in conscious sheep using strain-gauges and chronically implanted electrodes. Two hours after feeding the sheep, serotonin (5-HT) was infused into the jugular vein (i.v.), or the carotid artery (i.c.), or into the lateral cerebral ventricles (i.c.v.), over a 10-min period. An i.v. dose of 16 micrograms/kg/min abolished the cyclic propagated contractions throughout the forestomach, increased ruminoreticular tone, and induced simultaneous contractions of all the parts of the rumen. A dose of 1.6 micrograms/kg/min i.c. or i.v. 5-HT inhibited phasic contractions. The effects of 5-HT were blocked completely by i.c.v. administration of methysergide (20 micrograms/kg) and imipramine (200 micrograms/kg), and blocked partially by naloxone (25 micrograms/kg), but unaffected by atropine (50 micrograms/kg). The inhibitory effects of i.v. 5-HT were antagonized by methysergide (200 micrograms/kg, i.v.) but unaffected by imipramine (2 mg/kg, i.v.) and atropine (250 micrograms/kg, i.v.). Only the i.v. administration of methysergide blocked the inhibition induced by i.c. infusion (1.6 micrograms/kg/min) of 5-HT. It is suggested that 5-HT exhibits an inhibitory control on forestomach phasic contractions through hypothalamic and bulbar 5-HT receptors, and exerts peripheral excitatory effects on the tone of the rumen wall.