Pentobarbitone-anesthetized Rats Research Articles

Enhanced pronociception by amygdaloid group I metabotropic glutamate receptors in nerve-injured animals

Peripheral neuropathy has been associated with structural and functional changes of the amygdala, a key player in emotions. Here we study whether peripheral neuropathy influences pain regulation by the amygdala. For this purpose, we determined discharge rates of presumably pro- and antinociceptive pain-regulatory neurons in the rostral ventromedial medulla (RVM) following microinjection of various glutamatergic compounds into the central nucleus of the amygdala. RVM neurons were recorded in pentobarbitone-anesthetized rats with a peripheral nerve injury or sham-operation. In a separate behavioral experiment, we determined whether the influence of amygdaloid administration of a glutamatergic compound on affective pain-related behavior, as assessed by an aversive place-conditioning test, is changed by neuropathy. While glutamate or an NMDA receptor antagonist in the amygdala failed to induce marked changes in discharge rates of RVM cells, amygdaloid administration of DHPG, a group I metabotropic glutamate receptor (mGluR) agonist acting on mGluR 1 and mGluR 5, increased discharge rates of presumably pronociceptive RVM ON-cells in nerve-injured but not sham-operated animals. This pronociceptive effect of DHPG was reversed by MPEP (mGluR 5 antagonist) and CPCCOEt (mGluR 1 antagonist). CHPG, an mGluR 5 agonist, failed to influence ON-cell activity and DHPG failed to influence activity of presumably antinociceptive RVM OFF-cells. Amygdaloid administration of DHPG increased and that of CPCCOEt decreased affective pain-related behavior in nerve-injured animals. The results suggest that following nerve injury, the amygdaloid group I mGluR, particularly subtype mGluR 1, has an enhanced pronociceptive effect providing a potential mechanism for emotional enhancement of pain in peripheral neuropathy.

Convergence and Interaction of Hippocampal and Amygdalar Projections within the Prefrontal Cortex in the Rat

The orbital and medial prefrontal cortex (OMPFC) receives inputs from the CA1/subicular (CA1/S) region of the ventral hippocampus and the basolateral nucleus of the amygdala (BLA). Despite many studies about these projections, little is known as to how CA1/S and BLA inputs converge and interact within the OMPFC. Extracellular recordings of single-unit activity in the OMPFC were performed in sodium pentobarbitone-anesthetized rats. OMPFC neurons driven by CA1/S or BLA stimulation were more frequently encountered in the ventral portion of the prelimbic (v-PrL) and infralimbic cortex (IL). OMPFC neurons showing excitatory convergence of both inputs from the CA1/S and BLA were also located predominantly in the v-PrL and IL. The excitatory latencies of these neurons from both the CA1/S and BLA revealed almost identical values. Excitatory responses of OMPFC neurons to CA1/S (or BLA) stimulation were markedly augmented by simultaneous BLA (or CA1/S) stimulation, whereas the inhibitory influence of the BLA (or CA1/S) on CA1/S-induced (or BLA-induced) excitation was apparent when BLA (or CA1/S) stimulation was given 20-40 msec before CA1/S (or BLA) stimulation. Similar results were also observed when reciprocal connections between the CA1/S and BLA were severed to exclude the influences of these connections on one another. From these studies, we concluded that excitatory and inhibitory inputs from the hippocampus and amygdala converge and interact in the v-PrL and IL. Furthermore, the results indicate that simultaneous activation of hippocampal and amygdalar neurons may be important for amplification of OMPFC neuronal activity.

Comparison of the Visceral Antinociceptive Effects of Spinally Administered MPV-2426 (Fadolmidine) and Clonidine in the Rat

The authors determined the visceral antinociceptive effect induced by MPV-2426 (fadolmidine), a selective alpha 2 -adrenoceptor agonist, in rats with and without inflammation of the colon. They also determined whether the sympathetic nervous system or intact descending pathways are critical for the alpha 2 -adrenoceptor-induced visceral antinociception. Spinal neuronal responses evoked by colorectal distension were recorded in pentobarbitone-anesthetized rats. MPV-2426 was administered onto the spinal cord. Clonidine was used as a reference alpha 2 -adrenoceptor agonist. Inflammation of the colon was induced by turpentine. Sympathectomy was induced by 6-hydroxydopamine. A midthoracic transection of the spinal cord was performed to study the role of descending pathways. Spinal administration of MPV-2426 produced a dose-dependent attenuation of responses evoked by colorectal distension, and this effect was of the same percentual magnitude in inflamed as in noninflamed animals. Clonidine and MPV-2426 induced equipotent visceral antinociception. The effect by spinally administered MPV-2426 was enhanced by a chemical sympathectomy but not influenced by spinal transection. Spinally administered MPV-2426 produces a dose-dependent visceral antinociception as well in animals with an inflammation of the colon as in controls. The visceral antinociceptive effect induced by spinal MPV-2426 is equipotent to that of spinal clonidine. An intact sympathetic nervous system or intact brainstem-spinal pathway is not critical for the MPV-2426-induced visceral antinociception.

Modulation of visceral nociceptive responses of rat spinal dorsal horn neurons by sympathectomy.

We determined whether sympathectomy modulates visceral nociception under physiological or inflammatory conditions. Recordings of sacral spinal dorsal horn neurons with sustained responses were performed in pentobarbitone-anesthetized rats. Graded colorectal distension (CRD, 20-100 mmHg) was used as a visceral nociceptive stimulus. Inflammation was induced by intracolonic instillation of turpentine (25%). Sympathectomy was produced by administering 6-hydroxydopamine. Inflammation produced an increase in the CRD-evoked responses. The CRD-evoked responses were attenuated following sympathectomy both under control and inflammatory conditions. These changes in the CRD-evoked responses were associated with corresponding changes in spontaneous discharge rate. The convergent input evoked by noxious pinch of the skin was not changed by any of the experimental conditions. The results indicate that sympathectomy attenuates visceral nociceptive responses and spontaneous activity of sacral spinal cord neurons, without effect on convergent cutaneous inputs, both under physiological and inflammatory conditions.

Local Morphine Withdrawal Increases c-fosGene, Fos Protein, and Oxytocin Gene Expression in Hypothalamic Magnocellular Neurosecretory Cells

We measured stimulation of c-fos and oxytocin gene expression during excitation of oxytocin cells induced by systemic or local morphine withdrawal. Female rats were made morphine-dependent by intracerebroventricular morphine infusion over 5 d. Morphine withdrawal, induced by systemic injection of the opioid antagonist naloxone (5 mg/kg) in conscious or anesthetized rats, increased the density of c-fos messenger RNA and of oxytocin heterogeneous nuclear RNA in supraoptic nucleus cells compared with those of nonwithdrawn rats; c-fos messenger RNA was also increased in the magnocellular and parvocellular paraventricular nuclei of withdrawn rats. Morphine withdrawal increased the number of Fos-immunoreactive cells in the supraoptic and magnocellular paraventricular nuclei of conscious or pentobarbitone-anesthetized rats. Morphine withdrawal also increased Fos-immunoreactive cell numbers in the parvocellular paraventricular nucleus of conscious but not anesthetized rats. Central administration of the alpha(1)-adrenoreceptor antagonist benoxathian (5 microg/min) did not prevent morphine withdrawal-induced increases in the numbers of Fos-immunoreactive neurons in the supraoptic or magnocellular paraventricular nucleus. Unilateral microdialysis administration of naloxone (10(-5) M) into the supraoptic nucleus of anesthetized morphine-dependent rats increased Fos-immunoreactive cell numbers compared with the contralateral nucleus. Finally, we investigated whether dependence could be induced by chronic unilateral infusion of morphine into a supraoptic nucleus; systemic naloxone (5 mg/kg) increased Fos-immunoreactive cell numbers in the morphine-infused nucleus compared with the contralateral nucleus. Thus, morphine withdrawal excitation increases c-fos and oxytocin gene expression in supraoptic nucleus neurons. This occurs independently from excitation of their ascending noradrenergic inputs, and both dependence and withdrawal can be induced within the supraoptic nucleus.

Modulation of kainate-induced responses by pentobarbitone and GYKI-53784 in rat abducens motoneurons in vivo

The modulation of kainate-induced responses by pentobarbitone and the 2,3-benzodiazepine GYKI-53784 (LY303070), a potent non-competitive AMPA antagonist, was studied in vivo using both extracellular recordings of antidromic field potentials and intracellular recordings from abducens motoneurons in ketamine/diazepam-anesthetized rats. In previous studies on pentobarbitone-anesthetized rats [M. Ouardouz, J. Durand, GYKI-52466 antagonizes glutamate responses but not NMDA and kainate responses in rat abducens motoneurons, Neurosci. Lett. 125 (1991) 5–8; M. Ouardouz, J. Durand, Involvement of AMPA receptors in trigeminal postsynaptic potentials recorded in rat abducens motoneurons in vivo, Eur. J. Neurosci. 6 (1994) 1662–1668; A. Ruiz, J. Durand, Blocking the trigeminal EPSPs in rat abducens motoneurons in vivo with the AMPA antagonists, NBQX and GYKI-53655, J. Neurophysiol. (1998) submitted], we showed that 2,3-benzodiazepines do not affect kainate-induced depolarizations in abducens motoneurons. Here, we tested whether pentobarbitone is involved in the pharmacological discrimination by 2,3-benzodiazepines between AMPA- and kainate-induced responses. Kainate-induced depolarizations were reversibly depressed after application of either GYKI-53784 and pentobarbitone. However, kainate-induced depolarizations were not inhibited by GYKI-53784 with pentobarbitone; they were even potentiated sometimes. Using extracellular recordings, we confirmed that in the presence of pentobarbitone, GYKI-53784 counteracts the effects of AMPA but not of kainate on antidromic field potentials in the abducens nucleus. Blockade of kainate-induced responses by GYKI-53784 was reversed with pentobarbitone, which appears relevant to the discrimination between AMPA- and kainate receptor-mediated responses in vivo. In the presence of pentobarbitone, kainate would depolarize motoneurons mainly via kainate receptors since kainate-induced responses were not depressed by 2,3-benzodiazepines. This finding strongly favors the existence of kainate receptors in adult motoneurons but their role is still unknown.

Investigation into the effect of 5-hydroxytryptamine on fluid transport in the rat small intestine

1. 1. 5-Hydroxytryptamine (5-HT) has been shown to cause a consistent secretory effect in the rat small intestine only when administered luminally or by close intraarterial infusion. Intraluminal 5-HT-induced secretion is possibly mediated by 5-HT 4 receptors. Therefore, it was decided to investigate the effect of 5-HT and selective 5-HT 4 receptor agonists (SC 53116 and DAU 6236) on intestinal fluid transport in rat jejunum and ileum. The study also investigated the effect of a selective 5-HT 4 receptor antagonist (GR 113808) against the intraluminally administered 5-HT. 2. 2. 5-HT receptor agonists and antagonists were administered intraluminally in pentobarbitoneanesthetized rats. Changes in intestinal fluid transport across the intestinal wall were measured by a single pass technique. 3. 3. Intraluminal 5-HT produced significant antiabsorptive effects is both the jejunum and ileum. The 5-HT-induced responses were blocked by intraluminal administration of the 5-HT 4 receptor antagonist GR 113808. The 5-HT 4 agonist SC 53116 induced antiabsorptive effects in both regions of the small intestine, but DAU 6236 did not affect the rates of fluid transport. 4. 4. The results indicate that a 5-HT 4 receptor has a role in the luminal 5-HT-induced antiabsorptive effect on intestinal fluid transport in the rat.

Role of dorsal motor nucleus of vagus in gastric function and mucosal damage induced by ethanol in rats.

Experimental evidence indicates that the autonomic nervous system, especially the cholinergic pathway modulates the mucosal defensive mechanism and affects mucosal damage in the stomach. The present study investigated the role of the dorsal motor nucleus of vagus (DMV) in gastric function and its influences on ethanol-induced mucosal damage in pentobarbitone-anesthetized rats. Electrolytic lesion of the DMV as compared with sham operation and lesions of other brain areas, eg, nucleus reticular gigantocellularis and cuneate nucleus, reduced the basal gastric mucosal blood flow (GMBF) and also the blood flow after ethanol administration. The same operation did not affect the acid secretion either in the basal state or during the ethanol treatment period. Lesions at the caudal half of the DMV produced a bigger depression of GMBF when compared with lesion at the rostral half. In the sham-operated rats, ethanol induced severe hemorrhagic lesions in the gastric glandular mucosa, and this was significantly potentiated by lesions at the DMV, especially in the caudal half. The present findings indicate that acute DMV damage at the caudal half markedly affects the GMBF but not the acid secretion. The action on GMBF may contribute to the aggravation of ethanol-induced gastric damage in rats. These data reinforce the idea that the central vagal pathway, especially the caudal half of the DMV, plays a significant role in the modulation of GMBF, which in turn affects the integrity of gastric mucosal barrier.

Neuropeptide Y modulation of A1 noradrenergic neuron input to supraoptic vasopressin cells

A1 noradrenaline (NA) neurons provide a direct excitatory input to supraoptic nucleus (SON) vasopressin (VP) cells. Many A1 cells contain neuropeptide Y (NPY) and past studies have established that NPY exerts excitatory postsynaptic effects on VP cell activity. We have now investigated whether NPY might also modulate A1 input to VP cells via presynaptic mechanisms. Experiments done in pentobarbitone-anesthetized rats demonstrated that SON application of NPY (10 μM) excited VP cells but also depressed their response to activation of the A1 input. These two effects were not correlated, suggesting independent mechanisms. The putative Y 1 agonist [Leu 31,Pro 34]NPY (10 μM) also excited VP cells but did not alter their response to activation of the A1 input. In contrast, the putative Y 2 receptor agonist Ac-[Leu 28,Leu 31]NPY 24–36 mimicked the synaptic depression produced by NPY but did not significantly alter spontaneous activity. These data are consistent with the proposal that NPY acts on Y 1-like receptors to excite VP cells but can also act on a presynaptic Y 2-like receptor to depress A1-VP cell synaptic transmission.

Effects of Rat Bile Infusion on Renal Function in Rats

The influence of rat bile infusion on renal function in rats and the possible role of bile-induced hemolysis in these effects were examined. The hemolytic action of rat bile and some bile salts were determined in vitro. After the i.v. infusion of rat bile (70 mg freeze-dried powder/2.55 ml) into pentobarbitone-anesthetized rats, the urine, sodium and potassium excretion rates were reduced more than half, which was due to the decrease of glomerular filtration rate and increase of tubular water and sodium reabsorption. A fall in blood pressure, a rise in hematocrit, and hemolysis were also found. Infusion of hemolysed (30 microliters RBC) solution produced by distilled water and then made isotonic caused a short-duration increase in renal excretion and glomerular filtration rate, and the blood pressure was unchanged. Infusion of a rat bile-hemolysed solution after removal of bile acids with cholestyramine increased renal excretions at first with reduction thereafter. Infusion of the rat bile-hemolysed solution treated with barium sulfate produced a renal response very similar to rat bile alone. It is proposed that two factors are involved in the renal response after bile infusion, namely bile acid-induced hemolysis producing diuresis with natriuresis, and bile acid-induced antidiuresis and antinatriuresis, possibly due to a direct renal effect.

Salutary and Detrimental Effects of the (+)- and (−)Enantiomers of Meptazinol in Anesthetized Rats Subjected to Hemorrhagic Shock

The effects of the two enantiomers of the opioid mixed agonist-antagonist meptazinol on mean arterial pressure (MABP), heart rate (HR), and survival time were investigated in pentobarbitone-anesthetized rats subjected to hemorrhagic shock. Following intravenous administration of (+)meptazinol (0.5 mg kg-1) to shocked animals (MABP, 30.0 +/- 0.2 mm Hg), there was significant and gradual elevation of MABP, which at the time the experiment was terminated did not differ significantly from preshock values. In addition, survival was prolonged by up to 7 days. Paradoxically, similar doses of (-)meptazinol produced further falls in MABP, significantly so at 60 min posttreatment. Likewise, the drug produced a slow progressive and significant decline in HR which culminated in premature death (mean survival time, 74.3 +/- 5.9 min, compared with a control value of 104.4 +/- 8.8 min; p less than 0.05). Our results demonstrate that the two enantiomers of meptazinol have opposing effects on hemorrhagic shock sequelae in the rat. It is surprising, in view of its known opioid antagonistic properties, that (-)meptazinol exerted a detrimental effect.

Role of endogenous opioids on ventilation and chemical control of breathing in pentobarbitone-anesthetized rats.

To investigate the role of endogenous opioids on ventilatory control in pentobarbitone-anesthetized rats, the opioid antagonists naloxone and naltrexone were studied for their effects on ventilation, arterial blood gases and on ventilatory responses to hypoxia and carbon dioxide. In animals breathing room air, intravenous administration of naloxone and naltrexone (4 and 10 mg/kg) caused a dose-related increase in tidal volume, respiratory rate and minute volume. These ventilatory responses were rapid in onset and were associated with a decrease in arterial PaCO2, an increase in arterial pH and an increase in arterial PaO2. Intravenous naloxone (4 mg/kg) antagonized the increase in PaCO2 and decrease in arterial pH induced by the administration of morphine (3 mg/kg, i.v.). In animals breathing 100% O2, intravenous administration of naloxone and naltrexone (4 and 10 mg/kg) did not stimulate ventilation. Furthermore, intracerebroventricular administration of naloxone (15 and 150 micrograms) had no measurable effect on ventilation. Ventilatory responses to both hypoxia and carbon dioxide were not augmented by intravenous naloxone (4 mg/kg) and naltrexone (4 and 10 mg/kg). In fact, the increase in respiratory rate due to hypoxia was significantly (p less than 0.05) reduced by naltrexone (10 mg/kg, i.v.). In conclusion, our results demonstrate that naloxone and naltrexone caused hyperventilation in pentobarbitone-anesthetized rats. This effect was probably triggered by stimulation of the peripheral arterial chemoreceptors and did not involve mechanisms directly associated with the central nervous system. However, endogenous opioids were not involved in the chemical control of breathing in pentobarbitone-anesthetized rats since ventilatory responses to hypoxia and carbon dioxide were not changed by administration of these opioid antagonists.

Preferential release of oxytocin in response to vasoactive intestinal polypeptide in rats

Vasoactive intestinal polypeptide (VIP) was infused into the aorta of pentobarbitone-anesthetized rats (n = 12) in stepwise increasing doses of 0.001 to 10 μg/rat at rates varying from 0.3 pmol/min/kg to 3000 pmol/min/kg over 3 min. Blood was withdrawn from the vena cava inferior for the measurement of oxytocin (OT) and vasopressin (AVP) by RIA. The loss of blood was compensated for by infusion of isotonic saline (0.9% NaCl with 0.5% human serum albumin). Control rats received this solution only (n = 11). VIP infusions resulted in a dose-dependent increase in plasma OT which was significantly greater than the slight rise observed in the controls. The difference from controls was significant at infusion rates of 3 pmol/min/kg and more. Plasma AVP, on the other hand, did not rise in response to VIP infusions until the infusion rate was increased to 300 and 3000 pmol/min/kg. At these infusion rates, the increments in AVP were much smaller than those of OT, the levels during the highest infusion rates rising to 8.6 ± 2.8 and 27.2 ± 4.8 μU/ml, respectively (log normal means). The preferential release of OT in response to exogenous VIP in rats differs from the response in cats where intracarotid administration of VIP resulted in the release of proportionately more AVP than OT. Immunoreactive VIP is found in the hypothalamo-neurohypophyseal system of rats in close proximity of some of the magnocellular neurons as well as within the nerve terminals. This, together with our data, suggests that endogenous VIP may participate in the release mechanism for OT in rats.

Fusaric acid-induced elevation of homovanillic acid in the CSF as an index of brain noradrenaline synthesis

The effect of the dopamine-β-hydroxylase inhibitor, fusaric acid (FA), on cerebrospinal fluid (CSF) homovanillic acid (HVA) was studied in pentobarbitone-anesthetized rats. Idazoxan, a selective α 2-antagonist, accentuated the FA-induced HVA elevation in CSF while α-methyldopa pretreatment prevented this effect of FA on the HVA level in CSF. These results could indicate that the rate of dopamine synthesis in noradrenaline neurons could be the main determinant of the FA-induced HVA elevation.

Hypotensive activity of calcium entry blockers in rats. Relationship with depression of α2-adrenoceptor-mediated vasopressor responses

The hypotensive activity of a series of calcium entry blockers and various other vasodilators was quantified in pentobarbitone-anesthetized rats. Hypotensive activity was correlated linearly with the potency of these vasoactive agents to depress α 2-adrenoceptor-induced pressor responses in pithed rats. However, vasodilation as such also influenced α 2-adrenoceptor-mediated vasoconstrictor processes. For this reason, the depressive action of the vasodilating compounds on α 2-adrenoceptor-induced pressor effects was also determined during vasopressin infusion, which counteracted the vasodilation induced by the vasoactive compounds. It was found that the hypotensive activity exerted by the calcium entry blockers was directly related with their inhibitory activity to depress α 2-pressor responses. This relationship was not observed for the other vasodilators. The results provide further evidence for the hypothesis that vasodilatation induced by calcium entry blockers is caused by the selective impairment of that part of the vascular tone which is maintained by vascular postjunctional α 2-adrenoceptors.

Nomifensine antagonizes the ouabain-induced increase in dopamine metabolites in cerebrospinal fluid of the rat

The effect of the Na+, K+-ATPase inhibitor, ouabain, on cerebrospinal fluid dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) levels was studied in pentobarbitone-anesthetized rats. An intracerebroventricular injection of ouabain (100 nmol) dramatically increased DOPAC and HVA levels. A dopamine uptake inhibitor, nomifensine (10 mg/kg i.p.) injected prior to ouabain, completely abolished the effect of ouabain on dopamine metabolites. These results are in agreement with the ouabain-induced increase in dopamine efflux described in vitro and favour the role of a carrier-mediated cytosolic release of dopamine.

Ventilatory reflexes originated from carotid and extracarotid chemoreceptors in rats.

Ventilatory responses to transient stimulation and inhibition of arterial chemoreceptors--by hypoxia and hyperoxia, respectively--were studied in 10 pentobarbitone-anesthetized rats. N2 tests and intravenous injections of NaCN provoked transient increases in tidal volume and respiratory frequency, while O2 tests elicited decreases of these parameters. After bilateral carotid neurotomy, ventilatory responses to N2 and NaCN were still present although reduced in all rats, while ventilatory depression in response to O2 tests was observed in 60% of these rats. Further bilateral sectioning of main vagus, aortic, and superior laryngeal nerves immediately below the nodose ganglia abolished the ventilatory responses to NaCN in only one of the five rats subjected to this procedure, the remaining animals showing moderate hyperventilation in response to large doses of this drug. Mild ventilatory depression in response to hyperoxia, indicative of a persistent peripheral chemosensory drive, was still present in two of these rats. It is concluded that, although the carotid bodies constitute the main source of ventilatory chemoreflexes in rats, other vagally and nonvagally innervated chemoreceptors (presumably thoracic and abdominal) may elicit ventilatory reflexes in this species.

Cardiovascular and Respiratory Effects of β-Endorphin in Anesthetized and Conscious Rats

This study deals with the effects of beta-endorphin on blood pressure, heart rate, and respiratory frequency in anesthetized and conscious rats after both peripheral and central administration. Intravenous injection of beta-endorphin (40 and 160 micrograms/kg) in urethane-anesthetized rats resulted in a prolonged decrease in blood pressure, which, after the higher dose, was accompanied by bradycardia. In the pentobarbitone-anesthetized animals the same doses of beta-endorphin caused a small rise in blood pressure without affecting heart rate. No effect on respiratory frequency was observed. In urethane-anesthetized rats with hemorrhagic shock intravenous naloxone elicited a small pressor effect. Intracerebroventricular injection (i.c.v.) of beta-endorphin (40 micrograms/rat) in urethane-anesthetized rats resulted in severe respiratory depression and death. With lower doses there was a decrease in all parameters studied without ensuing death. Respiratory depression was even more pronounced in pentobarbitone-anesthetized rats, occurring with much lower doses of the peptide than in the urethane-anesthetized animals. beta-endorphin in the dose of 0.6 micrograms/rat still reduced respiratory frequency as well as heart rate without affecting blood pressure. Naloxone pretreatment antagonized the respiratory depression and death, while the decrease in heart rate was diminished. In conscious rats 10 microgram/rat, i.c.v., of beta-endorphin resulted in a decrease in heart rate and blood pressure without affecting respiratory frequency. It is concluded that beta-endorphin, or related opioid peptides, may be involved in cardiovascular and respiratory regulation. The effects of beta-endorphin, however, are markedly modified by the anesthetic agent used.

Local Noradrenaline Release in Acute Myocardial Ischemia

Left coronary artery ligations or sham operations were performed on pentobarbitone-anesthetized rats. The rats were sacrificed at various times after artery occlusion or sham operation and the creatine kinase (CK), potassium (K+), and noradrenaline (NA) content was determined in the left and right ventricular myocardium and in the interventricular septum. One group of rats was pretreated with the NA synthesis inhibitor alpha-methyl-p-tyrosine methyl ester (alpha-MT), another group with d,l-propranolol, and a third group with saline. The NA level of the ischemic left ventricle fell rapidly after the onset of ischemia. This early NA reduction was attenuated after alpha-MT treatment, probably due to reduced transmitter release. Both CK and K+ decreased in a time-dependent manner in the ischemic area of the heart. The early reduction of CK tended to be attenuated after alpha-MT as well as after propranolol. The results support the theory of a detrimental effect of locally released NA. However, in this model the injury produced by the extensive and nearly total ischemia seems so severe that the additional effect of myocardial adrenoceptor activation may well be only marginal.

Dopamine-induced ventilatory depression in the rat, mediated by carotid nerve afferents

In pentobarbitone-anesthetized rats, i.v. injections of dopamine (DA) at 10 −8–10 −5 g/kg led to transient ventilatory depression, usually not associated with changes in systemic arterial pressure. DA-induced ventilatory depression consisted of decreases in tidal volume and respiratory frequency in 12 rats, and in bradypnea without changes in tidal volume in 5 rats. After bilateral section of the carotid nerves, ventilatory responses to DA were abolished or greatly diminished. It is concluded that DA inhibits carotid body chemosensory discharges in the rat. The possibility that chemosensory activity directly affects respiratory frequency is discussed.