Pretreatment Of Cats Research Articles

Retraction：Pretreatment of Cats with Vitamin B6 Reduces Vomiting Episodes Following Xylazine Administration

Objective- Vomiting is a common problem of administration of xylazine in cats. This study was conducted to evaluate prophylactic antiemetic efficacy of vitamin B6 in sedated cats with xylazine. Design- Experimental study Animals- Eight adult cats (from both genders) were selected. Procedures- All the cats were administered with intramuscular injection of normal saline or four increasing dosages of vitamin B6 (5, 10, 20 and 40mg/kg) an hour prior to administration of xylazine with one week intervals. All the cats were monitored after injection of xylazine for thirty min to record the onset of first emesis, frequency of emetic episodes and the onset of recumbency. Results- Frequency of emetic episodes significantly decreased with each mentioned dosage of vitamin B6. Conclusions and Clinical Relevance- This study showed that pretreatment of cats with vitamin B6 may reduce episodes of xylazine induced emesis without compromising its sedative effect.

Retraction: Pretreatment of Cats with Vitamin B6 Reduces Vomiting Episodes Following Xylazine Administration

This article released online on September 26, 2012 as advance publication was withdrawn from consideration for publication in The Journal of Veterinary Medical Science at author's request.

Non-competitive-non-equilibrium alpha-adrenoceptor blocking properties of N-benzyl iodoacetamide, betsamide.

N-Benzyl iodoacetamide, betsamide, at 10 mg kg-1 i.v. blocked the hypertensive and contractile responses of the nictitating membrane of the cat to adrenaline. The blockade had a lag period before full development. Pretreatment of cats with betsamide for 7 or 18 h showed a non-equilibrium type of alpha-adrenoceptor blockade. The responses of the nictitating membrane to adrenaline were markedly depressed and did not recover after high doses of adrenaline. In the same cats, adrenaline caused a profound hypotension. The effect of betsamide lasted for at least 72 h. In the rat isolated vas deferens, 3 X 10(-5) M betsamide non-competitively blocked the contractile responses to noradrenaline; the adrenoceptor blockade was less effective when betsamide was applied with noradrenaline. The blockade lasted for more than 24 h, and was not reversible after extensive washing. Betsamide antagonized the contractile effects of carbachol and 5-hydroxytryptamine on the rat vas deferens, but not the beta-responses of the guinea-pig trachea to adrenaline and isoproenaline. Results are discussed in relation to a probable mechanism of action.

Do Renal Tubular Dopamine Receptors Mediate Dopamine-Induced Diuresis in the Anesthetized Cat?

The aim of this study was to investigate whether the pentobarbitone anesthetized cat is a suitable preparation in which to characterize renal tubular dopamine receptors. Intravenous infusion of dopamine (10-100 micrograms/kg/min) resulted in a dose-related increase in mean blood pressure (MBP), urine output, sodium excretion (UNaV), and fractional sodium excretion (FENa). This diuretic effect occurred despite little change in glomerular filtration rate, suggesting that it is a consequence of decreased tubular reabsorption. Dopamine (10-100 micrograms/kg/min, i.v.) also induced marked dose-related falls in renal vascular conductance; however, renal blood flow was not significantly reduced. The increases in MBP, urine output, UNaV, and FENa induced by dopamine (10-100 micrograms/kg/min, i.v.), were unaffected by pretreatment of cats with either the selective dopamine DA1 or DA2 receptor antagonists, SCH 23390 (30 micrograms/kg, i.v.), or domperidone (100 micrograms/kg, i.v.) respectively. In contrast, pretreatment of cats with the nonselective alpha-adrenoceptor antagonist, phentolamine (1 mg/kg, i.v.) prevented dopamine-induced increases in urine output and MBP. Infusion of the selective dopamine DA1 receptor agonist fenoldopam (0.01-10 micrograms/kg/min) into the left renal artery failed to increase left renal vascular conductance, or left kidney urine output, UNaV, or FENa. In conclusion, this study provides no evidence for the involvement of renal tubular dopamine receptors in dopamine-induced diuresis in anesthetized cats. Rather, the diuretic effect appears to be linked to stimulation of alpha-adrenoceptors.

Effect of interferon or Propionibacterium acnes on the course of experimentally induced feline infectious peritonitis in specific-pathogen-free and random-source cats

Summary Seventy-four cats (52 treated and 22 untreated) were evaluated in efficacy studies of interferon (ifn), Propionibacterium acnes, or a combination of these drugs against experimentally induced feline infectious peritonitis (fip). Cats were given doses of recombinant human leukocyte (α) ifn (rHuIFN-α), feline fibroblastic (β) ifn (FIFN-β) or P acnes at regular intervals before and after inoculation of virulent fip virus (fipv). Prophylactic and therapeutic administration of high doses (106 U/kg of body weight) or moderate doses (104 U/kg) of rHuIFN-α, FIFN-β (103 U/kg), or P acnes (0.4 or 4 mg) did not significantly reduce mortality in treated vs untreated cats. However, the mean survival time in cats treated with 106 U of rHuIFN-α-/kg alone or combined with doses of P acnes was significantly (P = 0.03) increased after inoculation of highly lethal amounts (200 LD100) of FIPV vs survival time in untreated cats. Although P acnes alone was ineffective, there was some indication that a combination of P acnes and high doses of rHuIFN-α was more effective than rHuIFN-α alone. Seemingly, the efficacy of rHuIFN-α treatment was improved in cats challenge-exposed with less fipv; in 1 trial, 4 of 5 cats (80%) treated with high doses of rHuIFN-α survived after inoculation of minimal lethal amounts (0.6 LD100) of fipv, whereas only 2 of 5 untreated cats (40%) survived. Pretreatment of cats with 106 U of rHuIFN-α/kg resulted in detectable serum ifn activity 24 hours later; serum ifn activity was not detected in cats pretreated with P acnes, fifn-β, or 104 U of rHulFn-α/kg. After inoculation of fipv, increase in serum ifn activity and virus-neutralizing antibody (vna) titer was observed in treated or untreated cats, but increase in serum ifn activity or vna titer was not associated with protective immunity. In contrast to untreated cats, those treated with high doses of rHuIFN-α had temporary suppression of clinical signs of fip and decreased serum ifn or vna responses to fipv, suggesting some antiviral or immunomodulatory (or both) activities. Immunomodulation by rHuIFN-α in cats inoculated with fipv also was suggested by necropsy findings of increased paracortical hyperplasia and decreased necrosis in lymphoid tissues of ifn-treated vs untreated cats. Results indicated that intensive treatment alone with ifn or P acnes failed to protect most cats against fatal disease after challenge exposure with lethal doses of fipv. High doses of rHuIFN-α alone or combined with P acnes, however, temporarily suppressed disease signs and extended survival time, suggesting a potential role of rHulFN-α as adjunctive, rather than primary, treatment for fip.

Endocrine influences on the detrusor of male and female cats

AbstractThe effects of ATP, adenosine (ADS), β,γ‐methylene ATP (APPCP), norepinephrine (NE), and hypogastric nerve stimulation (HGS) on urinary bladder responsiveness have been studied in male and female cats. Recent studies indicated binding sites for estradiol and testosterone in the urinary tract of animals. Other studies have demonstrated that estrogen alters the effects of certain agonists in urinary tract smooth muscle, although the mechanism of this effect is not known. The present study was designed to determine if differences occurred in the response of bladder smooth muscle in male vs. female cats to various stimuli and if surgical or drug pretreatment alters the response.The results of these experiments indicate differences between the response of the urinary bladder in female and male cats to various stimuli and that various pretreatments can alter the detrusor response to selected stimuli. In particular, detrusor of female cats was less responsive to most stimuli than detrusor of male cats, including stimuli that induced inhibition of pelvic‐nerve‐evoked bladder contractions (such as norepinephrine) and stimuli which induced bladder contractions (such as ATP). Also, gonadectomy altered the response of the detrusor making it more responsive to purine inhibitory stimuli, while having a mixed effect on detrusor responsiveness to excitatory stimuli. Pretreatment of cats with a gonadotropin‐releasing hormone antagonist also altered detrusor responsiveness, both inhibitory and excitatory agonists in a variable manner, increasing the magnitude of most responses. In addition to the above‐stated differences, the data also proved to underscore some similarities in the response of male and female cats to adrenergic and cholinergic stimuli. These studies imply that sex hormones influence detrusor response to certain purinergic stimuli and that alteration of sex hormone levels by surgery or medication can impact lower urinary tract function.

Role of lipid peroxidation in post-traumatic spinal cord degeneration: a review.

A large amount of biochemical, physiological, and pharmacological data has been obtained which supports a mechanistic role of oxygen free radical-induced lipid peroxidation (LP) in post-traumatic spinal cord degeneration. Biochemical evidence of early and progressive lipid peroxidative reactions occurring in the injured spinal cord includes: an increase in polyunsaturated fatty acid peroxidation products (e.g., malonyldialdehyde), a decrease in cholesterol and the appearance of cholesterol oxidation products, an increase in cyclic GMP presumably due to free radical activation of guanylate cyclase, a decrease in tissue anti-oxidant levels (e.g., alpha tocopherol, reduced ascorbate), and inhibition of membrane-bound enzymes such as Na+ + K+-ATPase. In vitro CNS tissue studies have provided support for the possibility that LP may contribute to other early post-traumatic events including intracellular calcium accumulation and arachidonic acid release. Moreover, spinal tissue lactic acidosis, which occurs early after injury, can exacerbate LP reactions. The involvement of LP in the development of progressive post-traumatic spinal white matter ischemia has been strongly inferred from pharmacological studies in cats with known inhibitors of LP. For example, the dose-response curves for the ability of the glucocorticoid methylprednisolone (MP) to inhibit post-traumatic LP and to retard ischemia development are identical. This relationship between LP and post-traumatic ischemia is more directly implied from studies showing that pretreatment of cats with high doses of anti-oxidants (e.g., d-alpha tocopherol plus selenium p.o. or 1-ascorbic acid i.v.) can also significantly antagonize the progressive decrease in spinal cord blood flow that follows severe blunt injury. However, a similar efficacy of certain calcium and prostaglandin antagonists suggests an interrelationship between aberrant calcium fluxes, vasoconstrictor/platelet aggregating prostanoids, and LP in the post-traumatic ischemic phenomenon. In addition to a role of LP in ischemia development, the action of intensive d-alpha tocopherol and selenium pretreatment to retard anterograde cat motor nerve fiber degeneration after nerve section suggests that LP may also be a fundamental mechanism of "Wallerian" axonal degeneration after neural injury. Finally, a critical role of LP in the acute pathophysiology of CNS injury in general has been supported by the finding of an excellent correlation, in terms of efficacy and potency, between the action of glucocorticoid and nonglucocorticoid steroids to inhibit neural tissue LP in vitro and to promote early neurological recovery in severely head-injured mice.

Cardioprotective effects of Defibrotide in acute myocardial ischemia in the cat

We investigated the effects of Defibrotide (D), a natural polydeoxyribonucleotide, on acute myocardial ischemia (AMI) in anesthetized cats. A permanent ligature was placed around the left anterior descending coronary artery (LAD) 12-14 mm from its origin. Ventricular fibrillation and death were exceptional and when they occurred the cats were not included in the evaluation. Pretreatment of cats with D, 32 mg Kg-1 h-1, i.v. infusion, maintained throughout the 5 h occlusion period, reduced AMI-ST segment increases and increased the diminished pressure-rate index (PRI). AMI-induced changes in lactate, ATP and CPK in ischemic tissue were prevented by D. PGI2 gave the same results as D. Atenolol prevented the loss of myocardial CPK, but had no favourable effects on lactate and ATP in ischemic tissue. The beneficial effects of D in AMI reported here could be partly attributed to its ability to enhance PGI2 release from vascular walls; D might also relieve ischemia by improvement of local tissue oxygenation, energy supplies and platelet function by its ability to deaggregate platelet clumps.

The Influence of Molsidomine and Its Active Metabolite SIN-1 on Fibrinolysis and Platelet Aggregation

Molsidomine and its active metabolite SIN-1 were examined in humans and animals for platelet suppressant and fibrinolytic activities. Following oral administration of molsidomine at doses of 6 or 15 mg/kg to rabbits, their blood platelets in PRP ex vivo required higher threshold concentrations of ADP, AA and thrombin to be aggregated. Unlike molsidomine, SIN-1 when infused (10 and 20 micrograms/kg i.v.) into anaesthetized cats caused a release of a substance disaggregating platelet clumps which had adhered to blood superfused collagen strip. The appearance of this unstable disaggregating substance was prevented by the pretreatment of cats with aspirin (50 mg/kg i.v.). It is suggested that SIN-1 may promote formation of a PGI2-like substance. In humans shortening of euglobulin clot lysis time was observed 60 min after a single ingestion of 2 mg of molsidomine. This fibrinolytic effect of molsidomine was not abolished by the pretreatment of patients with aspirin. Neither molsidomine nor SIN-1 activated fibrinolysis in preformed euglobulin clots in vitro.

Pharmacologic and Therapeutic Significance of ??-Adrenoceptor Subtypes

The concept that neurotransmitters can modulate their own release through presynaptic inhibitory autoreceptors is well established. The presynaptic inhibitory autoreceptors involved in a negative feedback mechanism that modulates the release of norepinephrine are of the alpha 2-subtype. Stimulation of central alpha 2-adrenoceptors by drugs like clonidine, guanfacine, and guanabenz produces an antihypertensive and bradycardiac effect through a decrease in sympathetic tone. In vascular smooth muscle, the alpha 1-adrenoceptor subtype predominates and mediates vasoconstriction although alpha 2-adrenoceptors mediating vasoconstriction are also present in some vascular beds. Phenylephrine preferentially stimulates alpha 1-adrenoceptors and guanabenz preferentially stimulates alpha 2-adrenoceptors in vascular smooth muscle, whereas norepinephrine is an agonist at both alpha 1- and alpha 2-subtypes. The pressor response to phenylephrine was markedly reduced by prazosin. In contrast, the response to norepinephrine was relatively resistant to blockade, and that to guanabenz, totally resistant to blockade by prazosin. Inhibition of neuronal uptake by cocaine or desipramine and pretreatment of cats with 6-hydroxydopamine increased the effectiveness of prazosin in blocking the pressor responses to norepinephrine, but not to guanabenz or phenylephrine. These results support the proposal that postsynaptic alpha 1-adrenoceptors are preferentially innervated (i.e., within the neuroeffector junction), while the postsynaptic alpha 2-adrenoceptors are in extrasynaptic locations. The subclassification of alpha-adrenoceptors into alpha 1- and alpha 2-subtypes opens the possibility of designing selective drugs to act as agonists or antagonists on these receptor subtypes. These compounds have useful therapeutic applications, and in the case of selective alpha 2-adrenoceptor antagonists, novel potential uses may exist, both at the level of the central nervous system and in the periphery.

Serotonergic and dopaminergic effects on yawning in the cat

The serotonergic agents LSD (0.01–0.05 mg/kg) and lisuride (0.025 and 0.05 mg/kg) elicited a high frequency of limb flicking in the cat after IP doses; LSD, but not lisuride, elicited a significantly increased frequency of yawning as well. In combination, LSD plus lisuride (0.25 mg/kg each) gave additive frequencies of limb flicking, but the frequency of yawning was half that after LSD alone. The dopamine agonist apomorphine had no significant effect on either yawning or limb flicking over the dose range 0.006 to 3.2 mg/kg. Pretreatment of cats with 1.0 mg/kg of apomorphine (but not with 0.05 mg/kg) significantly reduced the frequency of yawning elicited by 0.01 or 0.025 mg/kg of LSD, but had no effect of limb flicking. The dopamine antagonist haloperidol had no effect on limb flicking at doses from 0.008 to 0.512 mg/kg, but produced a significantly increased frequency of yawning at 0.256 mg/kg, an effect antagonized by lisuride administration. Given that lisuride has more potent dopamine agonist properties than LSD, these results are consistent with serotonergic elicitation of yawning, dopaminergic inhibition of yawning, and with their concomitant interaction in the expression of drug-induced yawning in the cat. The behavioral pharmacologies of limb flicking and yawning are different in this species.

Centrally mediated pressor response to metiamide as a result of gaba-receptor antagonism

M. J. Antonaccio, M. Asaad and J. Boccagno, Centrally mediated pressor response to metiamide as a result of GABA-receptor antagonism, European J. Pharmacol. 72 (1981) 369-372.The mechanism of the pressor response to metiamide was examined in anesthetized cats. Intravenous administration of metiamide had no effect on blood pressure. Infusion into the lateral ventricle (10 mg/kg/min for 10 min), caused a marked pressor response which was due to an increase in sympathetic outflow since pretreatment of cats with guanethidine completely prevented it. In a rat brain synaptosome preparation, both metiamide and cimetidine displaced [3H]GABA. These data strongly suggest that metiamide increases blood pressure in the cat through a central mechanism involving GABA-receptor antagonism.

Role of central dopaminergic receptors in manic response of cats to morphine.

The administration of morphine in conscious cats produces a manic response characterized by hyperexcitement and aggressive behaviour. This manic response was prevented by pretreatment of cats with either CNS catecholamine depletors (reserpine and tetrabenazine) or central dopaminergic receptor blocking agents eg. haloperidol and chlorpromazine. On the other hand, alpha and beta adrenergic receptor blocking agents-phenoxybenzamine and propranolol did not antagonise the morphine-mania. Similarly, anticholinergic (atropine), antihistaminic (mepyramine) and antiserotonin (LSD-25) agents did not prevent morphinemania. It is concluded that morphine releases dopamine in the CNS which in turn excites the central dopaminergic receptors to induce the manic response.

The influence of pargyline on the effects of in vitro dopamine infusions in the cat spleen

Infusions of dopamine into cat isolated perfused spleen preparations caused contractions of the capsule and increased the perfusion pressure. The infusions generally resulted in reduction of the responses of the spleen to nerve stimulation, but these reductions appeared not to be accompanied by a consistent decrease in the amount of noradrenaline released in response to nerve stimulation; it may have been accompanied by an increase in the amount of dopamine released. Pretreatment of cats with the monoamine oxidase inhibitor pargyline HCl failed to potentiate either the sympathomimetic effects of the in vitro dopamine infusions or their effects in reducing the responses of the spleen to nerve stimulation. Transmitter overflow also appeared to be unaffected by pargyline treatment. However, there was a 2-fold increase in the accumulation of the infused dopamine in the spleens from pargyline-treated cats. The results are discussed in the context of the hypothesis suggesting the involvement of dopamine as a “false” neurochemical transmitter in the antihypertensive effects of monoamine oxidase inhibitors.

Importance of adrenergic neurons of the brain for the rise of blood pressure evoked by hypothalamic stimulation.

The third ventricle and the aqueduct of the anaesthetized cat were cannulated and the hypothalamus was superfused with artificial cerebrospinal fluid. Electrical stimulation of the nucleus posterior of the hypothalamus elicited a rise of the blood pressure of 58±3 mm Hg (n=20). Superfusion of the hypothalamus with artificial cerebrospinal fluid containing bretylium (5×10−3 M) caused a gradual and long lasting impairment of the rise of blood pressure due to stimulation of the nucleus posterior. Tetracaine (1×10−3 M) diminished the rise of blood pressure to about the same extent as did 5×10−3M of bretylium; the inhibitory action of tetracaine was completely reversed within 120 min. Pretreatment of cats with 6-hydroxydopamine, which was applied through a Collison cannula implanted into the lateral ventricle, evoked a decrease of the noradrenaline content of the hypothalamus and of the rest of the brain and an impairment of the rise of blood pressure during stimulation of the nucleus posterior (33±3 mm Hg;n=6). The blood pressure of the anaesthetized cats was not affected by pretreatment with 6-hydroxydopamine. Superfusion of the hypothalamus with desipramine (1×10−4M) enhanced the rise of blood pressure elicited by electrical stimulation. The results are compatible with the assumption that the rise of blood pressure during stimulation of the nucleus posterior of the hypothalamus is mediated by adrenergic neurons of the brain.

Influence of pargyline on the effects of dopamine infusions on sympathetically innervated tissues

Pretreatment of cats with the monoamine oxidase inhibitor, pargyline HCl, potentiated both the sympathomimetic effects of intravenous dopamine infusions and the inhibitory effects of these infusions on the responses of the spleen and nictitating membrane to nerve stimulation. The potentiation of the inhibitory effects was not associated with an increase in the dopamine content, nor a decrease in the noradrenaline content, of the spleen, but was accompanied by an increase in the dopamine-noradrenaline ratio of the sympathetic transmitter released following nerve stimulation. The possible significance of these findings is discussed in the context of the hypothesis that the antihypertensive effects of monoamine oxidase inhibitors may be partially mediated through the involvement of dopamine as a “false” neurochemical transmitter.

Modification of the central hypotensive effect of α-methyldopa by reserpine, imipramine and tranylcypromine

In chloralase anaesthetised cats, α-methyldopa infused into the vertebral artery produces a hypotensive effect in doses that are ineffective peripherally. Pretreatment of cats with reserpine or imipramine blocks this effect whereas pretreatment with tranylcypromine greatly augments it. Tranylcypromine does not show this effect in animals pretreated with reserpine or imipramine.

Liberation of alpha-methyldopamine as a "false" sympathetic transmitter after pretreatment of cats with alpha-methyldopa and disulfiram.

Pretreatment of cats with α-methyldopa (3×200 mg/kg i.p. given over a period of 28 hrs) and simultaneous inhibition of dopamine β-hydroxylase by disulfiram (4×400 mg/kg p.o. given over a period of 44 hrs) diminished the norepinephrine content of the heart to 31% and of the spleen to 15% of control levels. The missing norepinephrine was only partially replaced by α-methyldopamine and the total catecholamine content of spleen and heart amounted to 51 and 70% respectively of untreated controls. In spinal cats the response of the nictitating membrane to sympathetic nerve stimulation was markedly diminished, whereas the effect of intravenously injected norepinephrine on blood pressure and nictitating membrane was considerably potentiated. In the isolated perfused spleen the contractile response to sympathetic nerve stimulation was also diminished and the pressor activity (expressed in terms of norepinephrine) of the venous effluent was reduced to 40% at a stimulating rate of 6/sec and to 39% at 10/sec. Together with the diminished amounts of norepinephrine α-methyldopamine appeared as a “false” sympathetic transmitter in the perfusion fluid. The two amines were liberated by sympathetic nerve stimulation in the same proportions in which they were stored in splenic tissue. From this and previous studies it becomes apparent that several aspects must be considered in correlating biochemical and functional findings: amounts of normal transmitter in tissues versus amounts liberated by sympathetic nerve stimulation, quantitative aspect of replacement of the physiological by the “false” transmitter in tissues and in the output from stimulated nerves, potency of the “false” transmitter at adrenergic receptors and its possible interference with transmitter inactivation.

Diminished effect of sympathetic nerve stimulation in cats pretreated with 5-hydroxydopa; formation and liberation of false adrenergic transmitters.

Pretreatment of cats with 5-hydroxydopa (3×200 mg/kg i.p., given over a period of 28 hours) resulted in a marked depletion of norepinephrine in sympathetically innervated organs (heart 5%, spleen 3%, iris 16% and nictitating membrane 12% of controls) and in a greatly diminished response of the spleen and nictitating membrane to sympathetic nerve stimulation. The decreased contractile response of the isolated perfused spleen was accompanied by a corresponding diminution of the norepinephrine output. The effect of intravenously injected norepinephrine on the blood pressure and nictitating membrane did not differ significantly from that of untreated controls. The chromatographic analysis of amines present in the spleen and heart after administration of 5-hydroxydopa and [3H]5-hydroxydopamine revealed the accumulation of 5-hydroxydopamine, of two not yet definitely identified β-hydroxylated metabolites (most probably the β-hydroxylated derivatives of 5-hydroxydopamine and of one of its O-methylated metabolites) and three O-methylated derivatives chromatographically identified as 4-methoxy-3,5-dihydroxyphenethylamine, 3-methoxy-4,5-dihydroxyphenethylamine and 3,4-dimethoxy-5-hydroxyphenethylamine. 5-Hydroxydopamine, its two β-hydroxylated and its two monomethoxylated metabolites were liberated as sympathetic transmitters. Their “direct” sympathomimetic effect (the β-hydroxylated derivatives were not available as references) on the nictitating membrane and spleen was 300–10000 times weaker than that of norepinephrine. It is concluded that the diminished contractile response of the nictitating membrane and spleen to sympathetic nerve stimulation results from a reduction of the physiological transmitter available for liberation and its replacement by less potent transmitter substances.

The effect of α-methyl-tyrosine on peripheral sympathetic transmission

Pretreatment of cats with α-methyl-tyrosine diminished the contractile response of the isolated perfused spleen to sympathetic nerve stimulation. Identical pretreatment did not influence the response of the nictitating membrane; a moderate reduction, however, occurred after longer pretreatment. The diminished contractile response of the spleen was accompanied by a diminished amount of norepinephrine in the venous effluent. The missing norepinephrine was replaced - though only to a small extent - by α-methyl-norepinephrine.