Colonic bead expulsion time in normal and mu-opioid receptor deficient (CXBK) mice following central (ICV) administration of mu- and delta-opioid agonists

A method utilizing the insertion of a 3 mm glass bead into the distal colon was used to evaluate the activity of intracerebroventricularly (ICV) administered mu- and delta-opioid agonists on colonic bead expulsion time in mice. Specifically, the ability of two mu-opioid receptor agonists, morphine and [D-Ala2,NMePhe4, Gly-ol5]-enkephalin (DAGO) and a selective delta-opioid receptor agonist, [D-Pen2,L-Pen5]-enkephalin (DPLPE), to inhibit colonic bead expulsion time was measured in normal (Swiss) and mu-opioid deficient (CXBK) mice. All three compounds maximally inhibited colonic bead expulsion time in normal mice. All three compounds also inhibited colonic bead expulsion time in CXBK mice, but none maximally. These results are in contrast to previous work in which clear differential analgesic sensitivity of CXBK mice to centrally administered mu- and delta-opioid receptor agonists was observed in the tail-flick test. Taken together, the results suggest (a) that mu-, and possibly delta-, opioid receptors can mediate supraspinal inhibition of colonic bead expulsion in mice and (b) that the genetic deficits of mu-receptor number or genetically-induced alteration in receptor function in CXBK mice do not equally affect inhibition of colonic bead expulsion and tail-flick antinociception.     

Biochemical characterization of FMRF-NH2-like peptides in spinal cords of various mammalian species using specific radioimmunoassays

Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (F-8-F-NH2) and Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala-Ala-Pro-Gln-Arg-Phe-NH2 (A-18-F-NH2), originally detected by FMRF-NH2 antiserum and subsequently isolated from bovine brain, were found to be highly localized in the bovine spinal cord. Using specific radioimmunoassays coupled with HPLC, F-8-F-NH2 and A-18-F-NH2 immunoreactivities in spinal cord of bovine, rat, mouse, guinea pig and human were studied. One major F-8-F-NH2 immunoreactivity was detected in the spinal cord of every species except in human, however, the retention time of F-8-F-NH2 immunoreactivity appears to vary from species to species. In the human spinal cord three major F-8-F-NH2 immunoreactivities are detected and one of them was eluted in the position of F-8-F-NH2. Two major A-18-F-NH2 immunoreactivities were detected in every species except guinea pig; one of these immunoreactivities can be identified as F-8-F-NH2 immunoreactivity due to the high affinity of the A-18-F-NH2 antiserum to F-8-F-NH2. F-8-F-NH2 and A-18-F-NH2 immunoreactivities can also be clearly detected by FMRF-NH2 antiserum, however, the quantities of these peptides can be grossly underestimated by the FMRF-NH2 RIA. These results confirm that there is a novel system of FMRF-NH2-like peptides in mammalian CNS and some of them are more closely related to the bovine peptides, F-8-F-NH2 and A-18-F-NH2 than to FMRF-NH2.     

Distribution and characterization of two putative endogenous opioid antagonist peptides in bovine brain

Highly sensitive radioimmunoassays were developed and used in studies of the distribution and chromatographic properties of two mammalian FMRF-NH2-like peptides recently isolated from bovine brain; an octapeptide with the structure Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (F-8-F-NH2) and on octadecapeptide, Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala-Ala-Pro-Gln-Arg-Phe-NH2 (A-18-F-NH2). F-8-F-NH2 and A-18-F-NH2 immunoreactivities are unevenly distributed in bovine brain. The highest concentrations (pmol g-1) of F-8-F-NH2 and A-18-F-NH2 are found in dorsal spinal cord (9.8 and 16.4 respectively), periaqueductal grey (8.6 and 6.8) and pons medulla (7.0 and 8.9); lowest quantities are in cortex, cerebellum and striatum. HPLC analysis coupled with radioimmunoassay reveals that the major immunoreactivities are identical to synthetic F-8-F-NH2 and A-18-F-NH2 while there are additional immunoreactive materials, distinct from NPY, whose structures still remain to be determined. The enrichment of these peptides in dorsal cord and periaqueductal grey, areas important in opioid-mediated pain perception, suggest that they may play a role in mediating antinociception.     

IgG from antiserum against endogenous mammalian FMRF-NH2-related peptides augments morphine- and stress-induced analgesia in mice

Two mammalian FMRF-NH2-like peptides have been isolated from bovine brain; an octapeptide with the structure Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (F-8-F-NH2) and an octadecapeptide, Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala-Ala-Pro-Gln-Arg-Phe- NH2 (A-18-F-NH2). In the present study determinations were made of the effects of intracerebroventricular administration of IgG prepared from antisera raised against these peptides on nociception and morphine- and immobilization-induced opioid analgesia in mice. Both F-8-F-NH2-IgG and A-18-F-NH2-IgG antisera increased nociception (thermal response latency) and significantly augmented morphine- and immobilization-induced analgesia in a naloxone reversible manner, with F-8-F-NH2-IgG antisera having a greater effect than A-18-F-NH2-IgG antisera. These results provide further evidence that mammalian FMRF-NH2-like peptides function as endogenous opiate antagonists and have a role in the mediation of antinociception.     

Blocking of cholecystokinin octapeptide behavioral effects by proglumide

An open field apparatus was used to assess the effect of proglumide, a selective antagonist of cholecystokinin octapeptide (CCK-8), to block the behavioral effect of CCK-8 in rats. Intracerebroventricular (ICV) injection of CCK-8 (0.5 to 2 micrograms) was effective in suppressing general exploratory activities and this effect was blocked by proglumide at doses of 2 to 5 micrograms administered ICV or 1 mg/kg administered subcutaneously. The effect of peripherally administered CCK-8 (10 micrograms/kg) was blocked by peripherally administered proglumide at a dose of 2 mg/kg but not by centrally administered proglumide at a dose of 5 micrograms/rat. The behavioral effect of CCK-8 was thus clearly blocked by proglumide.     

FMRF-NH2-like mammalian octapeptide: possible role in opiate dependence and abstinence

Yang et al. have isolated from bovine brain an octapeptide, FLFQPQRF-NH2 (F-8-F-NH2), with certain antiopiate properties. Malin et al. previously found that ICV injection of this peptide could precipitate an opiate abstinence syndrome in dependent rats. RIA revealed significantly higher levels of F-8-F-NH2 immunoreactivity in CSF withdrawn from the cisterna magna of morphine-dependent rats as opposed to CSF withdrawn from sham-implanted controls. ICV infusion of IgG from antiserum against F-8-F-NH2 significantly reduced the number of abstinence signs subsequently precipitated by naloxone in morphine-dependent rats.     

Neuropeptides and thermoregulation: the interactions of bombesin, neurotensin, TRH, somatostatin, naloxone and prostaglandins

In this study we have examined the interactions of bombesin (1 microgram ICV), neurotensin (1 microgram ICV), TRH (10 micrograms ICV), somatostatin (10 micrograms ICV), PGE2 (10 micrograms ICV) and naloxone (10 mg/kg SC) on thermoregulation in the rat at room temperature (20 +/- 1 degree C). Given alone, bombesin, neurotensin, somatostatin and naloxone all produced hypothermia (bombesin greater than neurotensin greater than somatostatin congruent to naloxone). PGE2 was hyperthermic, and TRH had no effect. Bombesin and PGE2 neutralized one another's effects. Neurotensin had no effect on PGE2-induced hyperthermia. Naloxone enhanced the hypothermic effect of bombesin and somatostatin enhanced the rate of onset of hypothermia after bombesin. TRH had no effect on bombesin-induced hypothermia. TRH, somatostatin and naloxone had no effect on neurotensin-induced hypothermia. TRH antagonized the hypothermia due to naloxone and somatostatin.     

Analog of neuropeptide FF attenuates morphine abstinence syndrome.

The octapeptide FLFQPQRFamide (neuropeptide FF or F8Fa) may play a role in opiate dependence and subsequent abstinence syndrome. Previously, NPFF precipitated opiate abstinence syndrome, while IgG from NPFF antiserum attenuated subsequent naloxone-precipitated abstinence signs in dependent rats. The peptide desamino YFLFQPQRamide (daY8Ra) was synthesized as a possible NPFF antagonist. At a dose of 600 ng ICV, daY8Ra significantly attenuated (p less than 0.001) the number of abstinence-like signs subsequently induced by 10 micrograms NPFF ICV, suggesting that daY8Ra does have antagonist activity against NPFF. Pretreatment of morphine-dependent rats with the same dose of daY8Ra also significantly attenuated (p less than 0.001) the abstinence signs subsequently precipitated by 10 micrograms naloxone ICV. Pretreatment with 600 ng of NPFF itself, or of NPFF modified at the N-terminal only (daY9Fa), failed to attenuate subsequent naloxone-precipitated abstinence, suggesting that the C-terminal modification is critical for NPFF antagonist activity. It should be noted, however, that higher doses of daY8Ra (2 micrograms or more) can precipitate some abstinence signs in a manner similar to NPFF.     

Influence of oxytocin on feeding behavior in the rat

Oxytocin, whether administered intraperitoneally (IP) (375-6,000 micrograms/kg) or intracerebroventricularly (ICV) (1-10 micrograms/rat), dose-dependently reduced food consumption and time spent eating and increased the latency to the first meal in rats fasted for 21 hr. Pretreatment with the oxytocin antagonist d(CH2)5Tyr(Me)-[Orn8]vasotocin (ICV 10 micrograms/rat) completely prevented the feeding inhibitory effect of an equal dose of ICV oxytocin, and per se increased food intake. Our data further support the hypothesis that oxytocin plays the role of neurotransmitter or neuromodulator in the CNS, and suggest that its involvement in a number of homeostatic systems may include appetite control.     

Effects of mammalian FMRF-NH2-related peptides and IgG from antiserum against them on aggression and defeat-induced analgesia in mice

The effects of two endogenous mammalian FMRFamide (Phe-Met-Arg-Phe-NH2)-related peptides, an octapeptide F8Fa (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) and an octadecapeptide A18Fa (Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala-Pro-Gln-Arg-Phe-NH2 ), and IgG from serum against them on the responses to aggression and defeat-induced analgesia were examined in subordinate mice in "resident-intruder" pairings. Intracerebroventricular (ICV) administrations of F8Fa and A18Fa (0.10-10 micrograms) reduced, in a dose-dependent manner, the number of bites to obtain defeat in the subordinate mice during the agonistic encounters, as well as attenuating defeat-induced analgesia, with F8Fa having a greater inhibitory effect than A18Fa. Peripheral administration of naloxone (1.0 mg/kg) had a similar inhibitory effect on the number of bites to defeat and the level of defeat-induced analgesia. In contrast, ICV administrations of F8Fa-IgG and A18Fa-IgG antisera increased the number of bites to defeat and augmented the levels of defeat-induced analgesia, with F8Fa-IgG having a greater effect than A18Fa-IgG. These results provide further evidence that the peptides, F8Fa and A18Fa, are involved in the modulation of opioid-mediated analgesia accompanying biological stressors and suggest that these endogenous FMRF-NH2-related peptides may also be associated with the expression of opioid-sensitive components of aggressive behavior.     

Vasopressin analgesia: specificity of action and non-opioid effects

Recent neuroanatomical and behavioral evidence has indicated that vasopressin (VP) increases pain thresholds. In the present study intracerebroventricular (ICV) administration of both arginine VP (AVP: 75-500 ng) and 1-deamino-8-D-arginine vasopressin (DDAVP: 150-500 ng) elevated tail flick latencies. Oxytocin (OXY, ICV), also elevated tail-flick latencies (150-1000 ng); however this increase was accompanied by "barrel-roll" seizure activity. VP analgesia was eliminated by pretreatment with 1-deamino-penicillamine-2(O-methyl)tyrosine-AVP (dPTyr(me)AVP: 500 ng, ICV), a VP antagonist, but not naloxone (1 or 10 micrograms, ICV), suggesting that VP modulates nonciceptive thresholds through its own binding sites. Conversely, pretreatment with naloxone (1 micrograms, ICV) but not dPTyr(me)AVP (1 microgram, ICV) attenuated the analgesic efficacy of systemic morphine (10 mg/kg), further dissociating VP and central opiate analgesic processes. Finally, systemic pretreatment with dexamethasone potentiated VP analgesia. These data support the notion that VP is a specific non-opioid pain inhibitor.     

Central effects of growth hormone-releasing factor (GRF) on intestinal motility in dogs: involvement of dopaminergic receptors

The effects of intracerebroventricular (ICV) and intravenous (IV) administration of human pancreatic growth hormone-releasing factor (hpGRF) on gastro-intestinal motility were examined in fasted and fed conscious dogs equipped with chronically implanted strain-gauges on the antrum and the jejunum. During the fasted state, hpGRF injected ICV at 0.1 micrograms . kg-1 or IV at 0.5 micrograms . kg-1 did not affect the cyclic occurrence of the migrating motor complex (MMC). This pattern was normally disrupted for 8-10 hours by a daily standard meal. Injected ventricularly (0.1 micrograms . kg-1) but not intravenously (0.5 micrograms . kg-1) 10-15 min after the daily meal, hpGRF significantly reduced (p less than 0.01) the duration of the jejunal fed pattern (2.0 +/- 1.4 vs. 8.4 +/- 1.1 hours for control) but not that of the stomach. This effect persisted when hpGRF (0.1 micrograms . kg-1 ICV) was administered after indomethacin (2 mg . kg-1 IM), naltrexone (0.1 mg . kg-1 IV) or domperidone (1 mg . kg-1 IV) but was abolished by a previous IV injection of metoclopramide (1 mg . kg-1). It was concluded that hpGRF is able to act centrally to control the pattern of jejunal motility in fed but not in fasted dog, its effect being probably mediated through dopaminergic pathways.     

Host plant resistance and linear furanocoumarin content of Apium accessions

Linear furanocoumarin contents and antibiotic resistance to Liriomyza trifolii (Burgess) were documented for Apium species being investigated in a celery breeding program. In no-choice tests, L. trifolii fed more, produced more offspring, and had the highest pupal and adult productivity on the widely planted cultivar 'Tall Utah' 52-70R (Apium graveolens L.). Antibiotic effects of the commercial cultivar 'Tall Utah' 52-70 HK and University of California families 87A-147 and 87A-338, derived from A. chilense Hook and Arn., were intermediate. Only A. nodiflorum (L.) Lag (accession 87A-236) did not allow survival beyond the larval stage. Concentrations of the carcinogenic and mutagenic linear furanocoumarins varied by location within plants (leaves usually greater than petioles), by specific compound (trend: psoralen less than xanthotoxin less than bergapten or isopimpinellin), and between accessions. A. nodiflorum had the lowest foliar levels of phototoxic furanocoumarins (11.8 micrograms/g fresh weight) and the best potential for use in the breeding program. Foliar levels of phototoxic furanocoumarins (psoralen, bergapten, and xanthotoxin) in plants 87A-147-3 (406 micrograms/g), 87A-147-2 (292.9 micrograms/g), and the family 87A-338 (265.9 micrograms/g) were 22.6, 16.3, and 14.8 times higher, respectively, than the concentration known to produce contact dermatitis (18 micrograms/g). Even with such variability in concentration, the foliar content of linear furanocoumarins (individually or total) and L. trifolii adult production were not correlated.     

Two sensitivity levels of cattle oocytes to puromycin

Germinal vesicle breakdown (GVBD) in cumulus-enclosed and denuded cattle oocytes was sensitive to puromycin at concentrations at or above 50 micrograms/ml. Media supplemented with 5-25 micrograms/ml of puromycin did not significantly reduce either rate or sequence of GVBD after 8 h of culture (82-96% GVBD). In concentrations of 50, 75, and 100 micrograms/ml, GVBD occurred in 15, 4, and 2% of oocytes, respectively. However, 50 micrograms puromycin/ml did postpone the time sequence of GVBD, since all treated oocytes underwent GVBD after 20 h of culture. Oocytes arrested in the germinal vesicle (GV) stage possessed GV filled with highly condensed bivalents. The puromycin block (100 micrograms/ml) was fully reversible, and the time sequence of GVBD was two times faster than in control medium. Proteins important for GVBD were synthesized during the first 4 h of culture, and 81% of oocytes underwent GVBD when puromycin (100 micrograms/ml) was added after 4 h of preincubation in control medium. The first polar body (I PB) expulsion was more sensitive to inhibition of protein synthesis, as shown by the observation that 2.5 and 5 micrograms puromycin/ml significantly (69 and 61%) reduced the incidence of Metaphase II, and 10 micrograms/ml highly significantly (31%) reduced it. The I PB expulsion in concentrations of 25 and 37 micrograms puromycin/ml was less than 5%. The subsequent culture in puromycin (8 h) and 6-dimethylaminopurine (8 h) proved that nuclear membrane breakdown is less sensitive to inhibition of protein phosphorylation than the process of chromatin condensation.     

Effects of intracerebroventricular injections of thyrotropin releasing hormone on gastrointestinal propulsive motility in rats

The effect of intracerebroventricular (ICV) injections of thyrotropin releasing hormone (TRH) on the propulsive motility of the gastrointestinal tract was examined in rats. The distance travelled by charcoal meal through the small intestine, measured in terms of percentage of its total length, was recorded as the index of propulsive motility. The results were as follows: (1) The propulsive distance of charcoal meal was significantly reduced in a dose-dependent manner after ICV injections of TRH (1 microgram/10 microliters, 5 micrograms/10 microliters or 10 micrograms/10 microliters) (P less than 0.01-0.001) The effects were abolished by injection of atropine (5 micrograms/10 microliters ICV). (2) The gastrointestinal propulsive motility decreased markedly (P less than 0.01) after injection of a larger dose of TRH (50 micrograms/100 g) into the hypodermis. The effects were not completely blocked by subcutaneous injections of propranolol (5 mg/kg). (3) No effects (P greater than 0.05) were found on the inhibition of gastrointestinal propulsive motility after ICV injections of regitine (2.5 mg/kg im, 50 micrograms/50 microliters ICV) or propranolol (5 mg/kg im, 50 micrograms/50 microliters ICV). The results indicate that TRH has an inhibitory effect on the propulsive motility of gastrointestinal tract, which may be mediated via the non-adrenergic inhibitory nerve of the vagal nerves.     

Autonomic effects of central injections of D-Ala2-Met-enkephalinamide (DAME) in the conscious monkey

The use of naloxone (NAL), an opioid receptor antagonist, has provided indirect evidence that endogenous opioids contribute to cardiovascular depression during shock. To determine if endogenous opioids act centrally to influence cardiovascular function, injections of D-Ala2-Met-enkephalinamide (DAME), a potent Met-enkephalin analog, were made into the 3rd cerebral ventricle (ICV) of 5 conscious cynomulgus monkeys restrained in primate chairs. Systolic blood pressure (SBP) and heart rate (HR) were determined every 10 min during a 30-60 min control period and for up to 5 hr post-injection. Colonic temperature (Tc) was monitored continuously. SBP declined from baseline values with 50 and 100 micrograms (85.2 and 170.4 nM) doses but was significant (p less than 0.001) for only the 100 micrograms dose between 15-125 min post-injection. HR also decreased but did not exhibit any significant variation with time. However, when averaged across time, HR fell significantly (p less than 0.001) from baseline: -9.1 +/- 2.3 and -15.0 +/- 2.1 b/min for 50 and 100 micrograms DAME, respectively. Tc displayed a nonsignificant, delayed (greater than 2 hr) rise in Tc with the 50 micrograms dose, whereas the 100 micrograms dose caused a significant (p less than 0.001) decline in Tc (from 65-125 min post-injection). NAL injected ICV attenuated the effects of DAME but had no effect on SBP, HR or Tc when injected alone. Systemic injection of DAME (300 micrograms) in one monkey produced a transient decline in SBP (26 mmHg within 2 min) which returned to baseline values 4 min post-injection. HR and Tc were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuropeptide Y depresses reflex urinary bladder contractions in rats and modifies central activity of opioid agonists

The 36 amino acid peptide neuropeptide Y (NPY) has been found distributed in central structures associated with nociception and the actions of opioid analgesics. We therefore studied its central actions on reflex bladder contractions which we have shown to be inhibited by supraspinal and spinal opioid administrations in urethane anesthetized rats. Neuropeptide Y produced a dose related (0.5-2 micrograms per rat) inhibition of bladder contractions following intracerebroventricular (ICV) and spinal intrathecal (IT) administrations. These effects could not be antagonized by naloxone (2 micrograms, ICV or IT) or by ICI 174,864 [N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH: Aib = alpha-aminoisobutyric acid] (3 micrograms, ICV or IT). NPY (0.5-1 micrograms) reduced the ICV and IT effects of morphine but potentiated the action of the selective delta-receptor ligand [2-D-penicillamine, 5-L-penicillamine] enkephalin (DPLPE). The effect of the mu-selective opioid ligand [D-Ala2, Me-Phe4, Gly(ol)5] enkephalin (DAGO) were unaffected as were the submaximal ICV and IT actions of noradrenaline. It was concluded that NPY-induced inhibition of bladder activity was not due to a direct opioid receptor interaction. However since NPY consistently changed the activity of opioids (morphine and DPLPE), this suggested a possible physiological role in the regulation of opioid receptors, central neural excitability and thereby visceral activity.     

Centrally administered atriopeptin III reduces water intake and vasopressin secretion in dehydrated sheep.

Two experiments were carried out to investigate the responses of sheep (N = 6) to intracerebroventricular (ICV) injections of atriopeptin III [atrial natriuretic factor (5-28), AP III]. In Experiment, 1, 24-h dehydrated animals were given 0 (saline vehicle control), 10 or 30 micrograms AP III directly before the presentation of water. The highest dose of AP III significantly (p less than 0.02) reduced the amount of water drunk in the subsequent 20 min. In Experiment 2, blood samples were taken at various intervals before and after ICV injection of 0 or 30 micrograms AP III when the sheep were water replete or 24-h dehydrated. Plasma concentrations of vasopressin (AVP) and cortisol were measured and estimates were made of plasma osmolality. In the dehydration condition, AVP levels were somewhat reduced (p less than 0.059) after AP III administration but no decrease was observed when the animals were euhydrated. No significant changes in plasma osmolality or cortisol concentrations were observed in response to AP III or the saline vehicle. Because a large dose of AP III (30 micrograms ICV) was required to produce the comparatively small behavioral and endocrine effects observed in this study, the results are suggestive of a pharmacological, rather than a physiological, action of the peptide in this species.     

Antagonistic effects of naloxone on CCK-octapeptide induced satiety and rumino-reticular hypomotility in sheep

Continuous intracerebroventricular (ICV) infusion of CCK-octapeptide (CCK8) was performed in ewes fitted with a permanent cannula into the lateral cerebral ventricle and Nichrome electrodes on the reticulum in order to record its electrical activity. In the first series of experiments, subsequently repeated in 12 h fasted animals, CCK8 was infused during the first hour of a 3 hour period of feeding at 2.5, 5 and 10 ng.kg-1.min-1. The same series of infusion were performed 20 min after ICV injection of 2.4 and 10 micrograms.kg-1 of naloxone. CCK8 reduced significantly in a dose related manner the food intake (r = 0.95; P less than 0.01) and the frequency of cyclic spike bursts associated to biphasic contractions of the reticulum observed during feeding (r = 0.89; P less than 0.01). At 5 and 10 ng.kg-1.min-1, the reduction of food intake reached 46.2 and 52.6% during the period of infusion; the basal and stimulated (feeding) frequency of reticular contractions were nearly halved. Previous ICV administration of naloxone (2.4 micrograms.kg-1) partially blocked the effects of CCK8 infusion on both food intake (72%) and reticular frequency (54% basal, 67% stimulated). The CCK8 induced effects on both food intake and frequency of reticular contraction were completely abolished after a previous 10 micrograms.kg-1 injection of naloxone. These results suggest that the central effects of CCK8 on feeding behavior and forestomach motility involve similar central structures and are mediated through opiate receptor structures.     

心房钠尿肽的中枢性心血管和肾效应

在麻醉大鼠观察了颈动脉、脊髓蛛网膜下腔和侧脑室内注射心房钠尿肽(Atrial natri-uretic peptide,ANP)后,血压,心率或/和尿量、尿钠和尿钾的变化,并观察了 ANP 对血管紧张素Ⅱ(AGⅡ)中枢效应的影响。结果如下:(1)在大鼠头部交叉循环条件下,经受血鼠颈总动脉内注射α-人心房钠尿多肽(α-human atrial natriurctic polypeptide,α-hANP)(15μg/kg)后,受血鼠平均动脉压(MAP)无改变,而供血鼠的 MAP 降低,⊿MAP为-2.4±0.84kPa(-18±6.3mmHg,P<0.05),(2)脊髓蛛网膜下腔注射心房肽,Ⅱ(AtriopeptinⅡ,APⅡ)(5μg/kg)对血压、心率和尿量无明显影响;(3)侧脑室注射 APⅡ(20μg/kg)后血压和心率无显著改变,尿量仅在注射后第30至50min 时显著增加,而尿钠无改变;(4)侧脑室注射 AGⅡ(1μg/kg),血压升高,⊿MAP 为1.3±0.17kPa(10±1.3mmHg,n=10,P<0.001)。注射1h 后,尿量增加106%(P<0.01),尿钠增加642%(P<0.01);(5)事先侧脑室注射 APⅡ(20μg/kg),2min 后再注入 AGⅡ(1μg/kg),AGⅡ的中枢升压效应不受影响,⊿MAP为1.5±0.25kPa(11±1.9mmHg,n=7,P<0.01),而尿量和尿钠的增值明显减小。以上结果表明,ANP 难于透过血脑脑脊血屏障,可能与其分子量较大有关。在静脉注射 ANP 所致降压效应中,似无中枢机制的参与。ANP 对 AGⅡ