Blocking action of decamethonium at different sites in the autonomic nervous system of the cat

Doses of decamethonium sufficient to paralyse skeletal and respiratory muscles in the cat for 20 to 30 min can reversibly block transmission at several sites in the autonomic nervous system. The sympathetic vasodilator outflow to skeletal muscle was blocked at the post-ganglionic nerve endings, probably by preventing the release of acetylcholine. The effects of vagal stimulation on heart-rate and intestinal contraction were blocked in most experiments, possibly by an action on pre-ganglionic as well as post-ganglionic nerve endings. However, decamethonium did not block all cholinergic nerve endings—for example, it did not diminish either the effects of stimulation of the chorda tympani on the submandibular salivary gland or those of pelvic nerve stimulation on the bladder.     

Histamine H3-receptors inhibit cholinergic neurotransmission in guinea-pig airways.

The histamine H3-agonist (R)-alpha-methylhistamine (alpha-MeHA) caused a dose-dependent inhibition of vagally-mediated contraction of a guinea-pig tracheal tube preparation but did not alter tracheal contraction induced by exogenously-applied acetylcholine. Blockade of H1- and H2-histamine receptors, and alpha- and beta-adrenoceptors failed to prevent the inhibitory effect of alpha-MeHA, whereas the specific H3-antagonist thioperamide prevented the effect of alpha-MeHA on tracheal contraction. In the presence of H1- and H2-receptor antagonists, histamine also inhibited vagally-mediated tracheal contraction. The inhibitory effect of alpha-MeHA was greater with preganglionic (vagus nerve) stimulation than with postganglionic stimulation by electrical field stimulation, suggesting that H3-receptors are localized both to cholinergic ganglia and to post-ganglionic nerve-endings. Our results suggest that H3-receptors exist on the vagus nerve which modulate cholinergic neurotransmission in the airways.     

A comparison of the effects of exogenous and endogenous prostaglandins on fast and slow contractions of field-stimulated guinea-pig vas deferens.

1. This study has compared the effects of exogenous and endogenous prostaglandins on the two phases of contraction of the guinea-pig vas deferens produced by electrical field stimulation. Prostaglandin E2 (PGE2), sulprostone and arachidonic acid dose-dependently and completely inhibited the first (fast) phase of contraction, with IC50s of 2.6 nM, 0.65 nM and 2.2 microM, respectively. 2. Following desensitization of the receptor for adenosine triphosphate (ATP) with alpha, beta-methylene ATP, PGE2, sulprostone and arachidonic acid dose-dependently inhibited the second (slow) phase of contraction of the guinea-pig vas deferens produced by electrical field stimulation, but the inhibition was incomplete (up to only 30%). Indomethacin (2.8 microM) reduced the effect of arachidonic acid. On its own, indomethacin (0.3 to 6.0 microM) had no consistent effect although, on some tissues, a slight potentiation of the contractions was seen. 3. Cicaprost (a PGI2 analogue) at low concentrations (0.5 to 30 nM) potentiated the first phase of contraction but even at high concentrations, had no consistent effect on the second phase of contraction of the guinea-pig vas deferens produced by electrical field stimulation. 4. PGE2, sulprostone and cicaprost potentiated contractions of the guinea-pig vas deferens produced by exogenous ATP. PGE2 and sulprostone also potentiated contractions produced by exogenous noradrenaline, whereas cicaprost had no consistent effect on the response to noradrenaline. 5. These findings indicate that prostaglandins of the E-series inhibit the second phase of contraction as well as the first phase of contraction of the guinea-pig vas deferens produced by electrical field stimulation. However, the extent of the inhibition is much less for the second phase than for the first phase. The reasons for this differential action of PGE are not clear. 6. Cicaprost potentiates the first phase but not the second phase of contraction. Since cicaprost potentiates the contractions produced by exogenous ATP, but not by exogenous noradrenaline, by an action presumably on post-junctional IP receptors, the potentiating action of cicaprost on the first phase of contraction produced by electrical field stimulation would appear to be satisfactorily explained through the action of cicaprost on these post-junctional IP receptors. 7. Exogenous arachidonic acid is apparently converted predominantly to PGE2 by the vas deferens, since the action of arachidonic acid mimicked that of PGE2 and was reduced by indomethacin. However, there was little evidence that sufficient PGE2 is generated during a short period (15 s) of sympathetic nerve stimulation for it to have any significant inhibitory effect on the size of the contractions produced.     

Physiological role of prostaglandins in adrenergic and non-adrenergic inhibitory neurotransmission in guinea pig taenia coli]

Prostaglandin (PG) E1, PGE2 and PGF2alpha and their biosynthesis inhibitor, indomethacin, were tested for their effects on the inhibitory responses of taenia induced by electrical stimulation of adrenergic and/or non-adrenergic inhibitory nerves in the perivascular nerve-taenia preparation isolated from guinea-pig caecum. The response to adrenergic nerve stimulation was considerably reduced by PGE1 and PGE2, while it was little affected by PGF2alpha. Although PGE1 and PGE2 produced contraction of taenia, it may be possible to dismiss from consideration their action of contraction of taenia in accounting for their inhibitory effect on the response to nerve stimulation since the following observations were made, 1) when the taenia were contracted by histamine, the response to adrenergic nerve stimulation was not reduced and 2) in the presence of polyphloretin phosphate, PGE1 and PGE2 did not contract taenia but reduced the response to adrenergic nerve stimulation. In the presence of indomethacin, the response to adrenergic nerve stimulation was increased greatly. On the contrary, the inhibitory response to non-adrenergic inhibitory nerve stimulation was not affected by application of PGE1, PGE2, PGF2alpha and indomethacin. These results suggest that endogenous PG of E series in guinea-pig taenia may play a role in modulating adrenergic neurotransmission. Attempts to demonstrate that PG could operate on a non-adrenergic inhibitory neurotransmission by a negative feedback mechanism were without success.     

Cooperation of ATP and norepinephrine in inducing contractile responses in guinea pig vas deferens

Stimulation of the hypogastric nerve to the guinea pig vas deferens induced biphasic contraction consisting of a rapid transient phase (mediated by ATP) and a delayed tonic phase (mediated by norepinephrine, NE), whereas stimulations in the presence of selective antagonists caused each contractile phase separately. Stimulation in the absence of antagonist induced a larger rapid transient contraction than that induced by stimulation in the presence of alpha 1-antagonist. Results obtained in separate or simultaneous additions of exogenous ATP and NE showed synergism in the rapid transient contraction. These findings indicate that NE assisted ATP in inducing the hypogastric nerve-mediated contractile response in guinea pig vas deferens, but not vice versa.     

色甘酸二钠抑制P物质能神经的作用

近来发现,P物质(SP)感觉神经在呼吸道内广泛分布,对呼吸道功能有重要影响,可引起支气管阻塞疾患的所有病理生理学改变。本文就色甘酸二钠(DSCG)抗哮喘作用与其对SP感觉神经的抑制作用之间相互关系进行了探讨。材料与方法DSCG和SP分别购于上海第四制药厂和上海东风生化试剂厂;SP拮抗剂(D-Arg~1,D-2,4-dicl_2-Phe~5,Asp~6,D-Trp~(7,9),Nle~(11))-SP由华东化工学院精细化工系提供。     

Contribution of prostaglandins to the activity of guinea-pig phrenic and chicken esophageal parasympathetic nerves

In order to clarify the role of prostaglandins (PGs) in the activity of cholinergic neurones other than the ileal myenteric plexus, the effects of indomethacin (IND) and PGE2 on the contractile responses and the release of acetylcholine (ACh) induced by electrical stimulation were investigated in isolated guinea-pig phrenic nerve-diaphragm and chicken parasympathetically innervated oesophagus preparations. In the guinea-pig phrenic nerve-diaphragm preparations, IND at 56 microM did not affect the twitch responses induced by direct or indirect electrical stimulation. PGE2 at 1 microgram/ml augmented the twitch responses induced by direct or indirect stimulation of submaximal, but not of supramaximal intensity. The amounts of ACh released from the phrenic nerve by electrical stimulation were unaffected by IND (56 microM). PGE2 (0.01-1 microgram/ml) inhibited the ACh release by the nerve stimulation of high frequency (50 Hz) in a concentration-dependent manner. The inhibitory effect of PGE2 was less clear on the ACh release by lower frequency (1 Hz). Neither IND nor PGE2 affected the ACh release induced by 40 mM-K+. In the chicken parasympathetically innervated oesophagus preparation, IND (2.8-5.6 5.6 microM) augmented the twitch responses induced by the nerve stimulation at a frequency of 0.017 Hz, but not those produced by train pulse (5 sec at a frequency of 1 or 10 Hz). This augmentation was reversed by the application of PGE2 at 10 ng/ml. PGE2 at 10 ng/ml produced a transient inhibition of the twitch responses induced by 0.017 Hz or train pulses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Participation of neuropeptides in antigen-induced contraction of guinea pig bronchi via NK(2) but not NK(1) receptor stimulation

We evaluated the contribution of neuropeptides to antigen-induced contractions of isolated bronchi and tracheae of passively sensitized guinea pigs using CP-96345 and SR 48968, specific antagonists of NK(1) and NK(2) receptors, respectively, in combination with treatment by an antihistaminic and a cysteinyl leukotriene antagonist. SR-48968 but not CP-96345, significantly inhibited the late phase of the bronchial contraction. Phosphoramidon, a neutral endopeptidase inhibitor, tended to potentiate bronchial contraction. Posttreatment with SR-48968 decreased the enhanced contraction induced by the inhibitor as well as the nonenhanced contraction to similar levels of tension. On the other hand, antigen-induced tracheal contraction was not altered by either neuropeptide antagonist. These results suggest that neuropeptides mediate the antigen-induced contractile response of the guinea pig bronchus partly through NK(2) receptor stimulation.     

Pharmacological actions of S-145, a novel thromboxane A2 antagonist, in various smooth muscles

Antagonistic actions of S-145 ((+-)-5(Z)-7-[3-endo[(phenylsulfonyl)amino]bicyclo[2.2.1] hept-2-exo-yl]heptenoic acid) against U-46619, a thromboxane A2 mimic, were studied using isolated thoracic aorta of the rat and the trachea, lung parenchyma and ileum of the guinea pig. S-145 as well as SQ-29548 and ONO-3708 inhibited the contraction of aorta induced by U-46619 in a concentration-dependent manner. The IC50 value of each compound was 1.4, 14.5 and 52.6 nM. S-145 also inhibited contractions of the aorta induced by high concentrations of PGE1, PGE2 and PGF2 alpha, but failed to affect the responses to K+, Ca2+, NE, 5-HT, and angiotensin II. Contractions of trachea and lung parenchyma of the guinea pig induced by U-46619 were concentration-dependently inhibited by S-145, but those induced by histamine and leukotriene D4 were not affected. Ileac contractions by PGE2 and PGF2 alpha were not inhibited by S-145. The (+)-isomer of S-145 was more potent and the (-)-isomer was less potent than S-145 for antagonistic action against U-46619. These results suggest that S-145 is a potent and specific antagonist to the thromboxane A2 receptor; and in the aorta, the thromboxane A2 receptor may respond to high concentrations of PGs.     

Effects of cooling on cholinergically-mediated contractions of tracheal muscle taken from immature and mature guinea pigs]

The tracheal strip-chain preparations taken from immature (less than 2 weeks old) and mature (greater than 16 weeks old) guinea pigs were used to study the cooling effects of bathing temperature on cholinergically-mediated contractions. In the tracheal muscles from immature animals, cooling of the bathing temperature from 37 degrees C to 20 degrees C augmented both the contractions induced by electrical stimulation (0.05-2 Hz, 0.6 msec, 150 mA) of intramural cholinergic nerves and contractions in response to acetylcholine (0.01-3 microM), while the cooling inhibited the carbachol (0.01-3 microM)-induced contractions. The pretreatment of the tissue with physostigmine (0.05 microM) also augmented both contractions induced by cholinergic nerve stimulation and those in response to acetylcholine (0.01-3 microM), but the cooling did not produce further augmentation of the responses. On the other hand, the tracheal muscles from mature animals showed a reduced contraction in response to cholinergic nerve stimulation by cooling, although the response was potentiated by the physostigmine pretreatment. Histochemical distributions of acetylcholinesterase activities were more marked in the tracheal muscles of immature guinea pigs than in mature ones. From these results, we conclude that increased responsiveness by cooling of the isolated immature guinea pig tracheal muscle to cholinergic nerve stimulation or exogenous acetylcholine may involve the decrease of intramural acetylcholinesterase activities which might be decreased age-dependently.     

Induction of stimulus-bound repetition in sympathetic ganglia by germine-mono-acetate

Germine-monoacetate (GMA) induces stimulus-bound repetition (SBR) in frog sympathetic ganglia which is not suppressed by concentrations of d-tubocurarine that selectivity suppress SBR elicited by anticholinesterases. SBR elicited by pre-ganglionic stimulation occurred at a lower thershold concentration of GMA, was more readily suppressed by large concentrations, and was less prominent at higher stimulus frequencies than SBR following post-ganglionic stimulation.     

The presynaptic activity of huwentoxin-I, a neurotoxin from the venom of the chinese bird spider Selenocosmia huwena.

Three different types of isolated nerve-synapse preparations, guinea pig ileum, rat vas deferens and toad heart, were used to investigate the physiological activity of Huwentoxin-I, a neurotoxin from the venom of the spider Selenocosmia huwena. The twitch response of isolated guinea pig ileum induced by electrical stimulus can be inhibited by HWTX-I. After blockage, contraction of the ileum can be induced by exogenously applied acetylcholine. HWTX-I caused the inhibition of the twitch response to electrical nerve stimulation in the rat vas deferens. After the twitch was completely inhibited, noradrenaline triggered rhythmic contraction of the vas deferens. The inhibitory effect on heart of toad induced by stimulating sympathetic-vagus nerve can be reversed by HWTX-I, although exogenously applied acetylcholine still acts as an effective inhibitor. All of these results support the conclusion that HWTX-I has the presynaptic activity that effects the release of neurotransmitter from the nerve endings of both the cholinergic synapse and the adrenergic synapse.     

Pharmacological studies with the alpha 2-adrenoceptor antagonist midaglizole. Part II: Central and peripheral nervous systems.

Pharmacological properties of midaglizole (DG-5128, CAS 66529-17-7) on central and peripheral nervous systems were investigated in comparison with those of tolbutamide. 1. Central nervous system: Midaglizole showed little or no effects on general behavior (mouse), spontaneous motor activity (mouse), hexobarbital anesthesia (mouse), conditioned avoidance response (rat) and body temperature (rabbit) at an oral dose of 100 mg/kg. It also produced little or no changes in electroencephalogram (cat) and spinal reflex (cat) after intravenous dosing of 10 mg/kg. The drug lacked anticonvulsant and analgesic activities (mouse). Midaglizole produced clonic convulsion, mydriasis, lacrimation, increase in pinna reflex, decrease in spontaneous motor activity, increase in pain threshold (mouse) and rise in body temperature (rabbit) at oral dose of 300 mg/kg. Tolbutamide showed similar effects except that it potentiated hexobarbital anesthesia, slightly decreased convulsion and tended to decrease body temperature. 2. Autonomic nervous system: Midaglizole potentiated the pressor response to norepinephrine and inhibited the depressor response to acetylcholine at an intravenous dose of 10 mg/kg (anesthetized dogs). Similar results were observed after dosing of tolbutamide. Midaglizole potentiated the contractile response of nictitating membrane to pre- and post-ganglionic cervical sympathetic nerve stimulation after intravenous dosing of 1 mg/kg (cat). Tolbutamide lacked the activity on the contraction elicited by both stimulations. Midaglizole and tolbutamide had little or no effect on pupil size (rabbit). 3. Skeletal muscle contraction (neuromuscular junction): Midaglizole (3-10 mg/kg i.v.) slightly potentiated the tibialis anterior muscle contraction induced by peroneal nerve stimulation, but did not potentiate the contraction by direct (muscle) stimulation (rabbit). On the other hand, tolbutamide increased the contraction induced by both nerve and muscle stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibitory effect of 2-(2-fluoro-4-biphenylyl)propionic acid (Flurbiprofen) on prostaglandin synthesis]

Inhibitory effects of 2-(2-fluoro-4-biphenylyl) propionic acid (Flurbiprofen, FP-70) on prostaglandin (PG) synthesis and PG activity were investigated both in vivo and in vitro. FP-70 at 0.64 micronM showed 50% inhibitory effect on PG synthesis from arachidonic acid in cell-free homogenate of guinea pig lung. PGE2 and PGF2alpha in the sample of lung homogenate incubated with arachidonic acid were separated by thin-layer chromatography in solvent AI system. FP-70 inhibited strongly both synthesis of PGE2 and PGF2alpha at 3 micron, but inhibited more extensively the synthesis of PGE2 than that of PGF2alpha at 0.3 micronM. FP-70 at 1 mg/kg, p.o. inhibited mostly arachidonic acid potentiation of carrageenin-induced edema in the rat paw, but did not inhibit PGE2 potentiation of carrageenin-induced edema. FP-70 also did not inhibit the contraction of rat stomach strip induced by PGE2. From the above and previously5) reported results, FP-70 proved to inhibit PG synthesis but not PG activity. It is suggested that the potent anti-inflammatory action of FP-70 is the result of inhibition of PG synthesis.     

Effects of anti-asthma drugs and potassium channel openers on neurally-mediated contraction of isolated guinea pig trachea.

The effects of anti-asthma drugs, isoproterenol, aminophylline and hydrocortisone, and potassium channel openers on the contraction induced by electrical stimulation or exogenously applied acetylcholine were investigated in isolated guinea pig trachea. Isoproterenol and aminophylline non-selectively inhibited both the contraction evoked by vagus nerve- and that by transmural field-stimulation, but had no effect on the response induced by exogenously applied acetylcholine. Hydrocortisone and potassium channel openers, NIP-121 and cromakalim, preferentially inhibited vagus nerve-mediated response. These results suggest that anti-asthma drugs may have an ability to inhibit neurally-mediated contraction in the guinea pig trachea.     

Effects of oxybutynin hydrochloride on the urinary bladder and urethra in in situ preparations

Effects of oxybutynin on the urinary bladder and urethra were studied in comparison with atropine and flavoxate in cats and rabbits. Oxybutynin at 10 mg/kg, i.v., significantly inhibited the bladder contractions induced by electrical stimulation of the peripheral end in pelvic nerve. Oxybutynin was about one half the potency of atropine. On the contrary, 10 mg/kg of flavoxate, i.v., showed both effects of potentiation and inhibition. The bladder contractions induced by acetylcholine (ACh) and AHR-602 were markedly inhibited by oxybutynin and atropine. Oxybutynin was about one-fifteenth the potency of atropine. DMPP-induced contractions were inhibited by oxybutynin and atropine in a high dose, but oxybutynin was about two-fifths the potency of atropine. In addition, 3 mg/kg of oxybutynin, i.v., inhibited the contraction induced by hypogastric nerve stimulation, but 10 mg/kg of oxybutynin, i.v., significantly inhibited this contraction following initial potentiation. Oxybutynin showed an inhibitory effect on spontaneous rhythmical contraction, bladder tone and pelvic nerve discharge, similar to the effects of atropine. On the contrary, flavoxate potentiated this contraction and increased the bladder tone and pelvic and hypogastric nerve discharge. Urethra contractions induced by norepinephrine, ACh and hypogastric nerve stimulation were inhibited by oxybutynin, but not markedly. Oxybutynin and atropine dose-dependently increased the infusion volume, bladder volume capacity and micturition threshold pressure in the cystometrogram in rabbits. Flavoxate also increased them. From these results, it si suggested that oxybutynin is therapeutically a useful agent for pollakisurea nervosa.     

Sympathetic vasodilatation in the rabbit ear

Changes in the blood content of a 1 cm² portion of the intact rabbit's ear were studied with transillumination and a photocell. Stimulation of the post-ganglionic sympathetic nerves produced a decrease in blood content, attributable to vasoconstriction, followed by an increased blood content, attributable to vasodilatation. The vasodilatation was enhanced by eserine and decreased by atropine. Guanethidine abolished the vasoconstriction but not the vasodilatation. After the ganglion had been decentralized by degeneration of the pre-ganglionic sympathetic nerves the vessels had an increased sensitivity to acetylcholine and the vasodilatation in response to sympathetic stimulation was enhanced. It is concluded that sympathetic stimulation results in the liberation of acetylcholine which causes vasodilatation.     

Inhibition of the contraction of the isolated longitudinal muscle of the guinea-pig ileum by botulinum C2 toxin: Evidence for a role of G/F-actin transition in smooth muscle contraction

Summary The effect of botulinum C2 toxin was studied on the contractions of the guinea pig ileum myenteric plexus longitudinal muscle preparation. Botulinum C2 toxin inhibited the muscle contraction induced by electrical stimulation (60 V; 0.5 ms; 0.33 Hz) in a time and concentration dependent manner. The inhibitory effect occurred with a time lag of about 1 h, and depended on the presence of both toxin components. After 4 h of incubation with 1.7 µg/ml of component I and 6.7 µ/ml of component II of botulinum C2 toxin, the smooth muscle contraction was inhibited by about 60%. At these toxin concentrations, about 55% of the modifiable smooth muscle actin was ADP-ribosylated. Smooth muscle contraction induced by bradykinin and bethanechol were similarly inhibited. Moreover, the C2 toxin inhibited muscle contraction induced by Bat²⁺, and by direct muscle membrane depolarization (60 V; 10 ms; 0.33 Hz) after suppression of acetylcholine release by normorphine. Also cytochalasin D inhibited the electrically evoked contraction of the ileum longitudinal muscle. In contrast to botulinum C2 toxin, inhibition of contractility by cytochalasin D occurred without a lag phase, and was reversed by washing off the toxin. In contrast of guinea pig ileum longitudinal muscle, botulinum C2 toxin did not reduce the contraction of the rabbit aortic smooth muscle stimulated by K⁺-depolarization or noradrenaline. Send offprint requests to K. Aktories at the above address     

Elucidation with the protease alpha-chymotrypsin of the inhibitory modulating action of endogenous neuropeptide Y over sympathetic neurotransmission in rat vas deferens

The physiological role of endogenous neuropeptide Y (NPY) in sympathetic neurotransmission was examined in rat and guinea pig vas deferens (VD), using alpha-chymotrypsin (alpha-CT). NPY-like immunoreactivity was detected in the longitudinal muscle layer of VD densely in rats but sparsely in guinea pigs, and it disappeared following surgical denervation. Under blockade of the prejunctional alpha(2)-adrenergic autoinhibition, alpha-CT potentiated the phasic contraction in rat, but not guinea pig, VD induced by trains of transmural nerve stimulation (TNS) in a frequency-dependent manner, which was reproducible during repeated applications and not affected by pretreatment with capsaicin. In contrast, alpha-CT did not potentiate the twitch response or contractions induced respectively by a single pulse TNS or by direct electrical stimulation to the smooth muscle. Exogenously applied NPY suppressed the twitch response, which was cancelled by alpha-CT, and excitatory junction potentials, although it affected neither spontaneous junction potentials nor the direct electrical stimulation-induced contraction. These observations provided further evidence to support that NPY is released endogenously by TNS at high frequency, acting prejunctionally to suppress sympathetic neurotransmission. Thus, the protease alpha-CT proved itself to be a useful tool to reveal a functional role of endogenously released peptides.     

Effects of ketamine on the peripheral autonomic nervous system of the rat.

The effects of ketamine (2-(o-chlorophenyl) 2-methylaminocyclohexanone) (2-50 mg/kg) on the responses of the pithed rat arterial pressure, anococcygeus muscle and colon to selective stimulation of the spinal autonomic outflows were examined. Ketamine depressed the vasopressor response produced by stimulation of the lumbar sympathetic outflow in a dose-dependent manner but did not significantly affect the pressor response to intravenous noradrenaline (NA) administration. Ketamine depressed the motor responses of the anococcygeus to stimulation of the pre-ganglionic lumbar sympathetic outflow or to stimulation of post-ganglionic fibres in the sacral region in a dose-dependent manner, the response to preganglionic stimulation being relatively more sensitive to such depression. The anococcygeus response to NA was significantly potentiated with doses of ketamine of 20 mg/kg and 50 mg/kg. Ketamine depressed the motor response of the smooth muscle of the colon to stimulation of the sacral parasympathetic outflow in a dose-dependent manner and at lower doses than were required to produce an equivalent depression of the sympathetic responses in the other tissues. A comparison was made of the effects of ketamine and cocaine on the motor responses of the anococcygeus muscle in vitro to NA, carbachol and field stimulation. Both ketamine and cocaine produced a non-specific depression of all responses at high doses whereas cocaine but not ketamine produced a large potentiation of NA and motor nerve responses at lower doses. The results are discussed in relation to the hypothesis that ketamine might elevate blood pressure in conscious animals and man by potentiating vascular adrenergic responses.