Studies on the hypotensive action of alpha-methyldopamine.

1. Intraventricular alpha-methyldopamine (50-200 mug) produced a dose-related fall in blood pressure in conscious spontaneously hypertensive rats. Pretreatment with intraventricular 6-hydroxydopamine prevented this hypotensive effect of alpha-methyldopamine. 2. The hypotensive effect of alpha-methyldopamine was prevented by intraventricular injection of phentolamine or desmethylimipramine, but not by intraperitoneal injection of haloperidol. 3. Pretreatment with U-14,624, a selective central dopamine-beta-hydroxylase inhibitor, prevented the hypotensive effect of alpha-methyldopamine. 4. Alpha-methyldopamine was considerably less potent than noradrenaline as a pressor agent in the pithed rat, but noradrenaline and alpha-methylnoradrenaline were found to be equipotent. 5. Alpha-methyldopamine (1-5 mg i.c.v.) reduced pressor responses elicited by electrical stimulation of the midbrain reticular formation in cats anaesthetized with chloralose. 6. It is concluded that the hypotensive action of alpha-methyldopamine in conscious animals involves intact central alpha-adrenergic neurones and a central adrenergic uptake mechanism for the formation of alpha-methylnoradrenaline.     

INHIBITORY EFFECT OF FRUSEMIDE ON SYMPATHETIC VASOCONSTRICTOR RESPONSES: DEPENDENCE ON A RENAL HORMONE AND THE VASCULAR ENDOTHELIUM

1. Mesenteric perfusion pressure was measured in the in situ mesentery perfused at a constant rate with blood drawn from the carotid artery of the same anaesthetized rat. Increases in perfusion pressure were produced by mesenteric periarterial electrical stimulation. These responses were measured before and 30 min after the administration of frusemide (5 mg/kg i.v.) to the rat. Loss of volume due to the frusemide-induced diuresis was prevented by a urinary bladder-venous extracorporeal circuit. 2. Responses to stimulation were reduced after frusemide and were not increased by the subsequent administration of indomethacin (2 mg/kg i.v.). This indomethacin treatment rapidly and completely prevented the fall in blood pressure produced by i.v. arachidonic acid. 3. In rats where the renal papilla had been ablated by treatment with bromoethylamine (200 mg/kg i.p.) 5 weeks previously, frusemide administration did not reduce sympathetic responses in the in situ blood-perfused mesentery. 4. A segment of rat tail artery, cannulated at both ends was mounted in an organ bath and perfused with blood withdrawn from, and returned to, an anaesthetized rat. Increases in perfusion pressure produced by periarterial electrical stimulation of this ex vivo blood perfused tail artery segment were reduced by frusemide administration to the anaesthetized rat. 5. When the endothelium was removed from the tail artery segment, frusemide administration did not lead to any reduction of vasoconstrictor responses. 6. Frusemide may lead to the release of a non-prostanoid hormone from the renal medulla which results in inhibition of peripheral sympathetic vasoconstrictor responses. The release of the hormone may involve intra-renal prostaglandins. The final antivasoconstrictor effect requires an intact vascular endothelium.     

Effect of alpha-methyldopa on sympathetic nerve function in the pithed rat

Pressor responses induced by stimulation of the entire sympathetic outflow in the pithed rat were unaffected by acute dosage with α-methyldopa, 200 mg/kg i.p. but significantly reduced on sub-chronic dosage. α-Methyldopa markedly reduced the positive chronotropic effects evoked by noradrenaline, α-methylnoradrenaline and stimulation of sympathetic cardiac nerves. α-Methyldopa-induced antagonism of cardiac acceleration is due to depressed pacemaker sensitivity to noradrenaline and α-methylnoradrenaline.     

A comparison of the effects of chemical sympathectomy by 6-hydroxydopamine in newborn and adult rats

1. The effects of chemical sympathectomy with 6-hydroxydopamine (6-OHDA) on the cardiovascular system of the rat were compared in, (a) 10-week-old rats treated during the first 14 days after birth with 150 mug/g subcutaneously, and (b) adult rats injected intravenously with 2 x 50 mg/kg on day 1 and 2 x 100 mg/kg on day 7 and the experiments performed on day 8.2. Intravenous administration of 6-OHDA to adult rats almost completely abolished the pressor responses to stimulation of the entire sympathetic outflow in the pithed rat, the contractions of the lower eyelid to stimulation of the cervical sympathetic trunk and the vasconstrictor responses produced by periarterial nerve stimulation of the isolated renal artery preparation. Pressor responses to physostigmine and to tyramine were markedly reduced or abolished in anaesthetized and pithed rat preparations, respectively.3. In corresponding experiments, 10-week-old rats treated as newborns with 6-OHDA showed a marked reduction in the stimulation-induced pressor responses and contractions of the lower eyelid, but completely normal vasoconstrictor responses to periarterial nerve stimulation of the isolated perfused renal artery were obtained. The pressor responses to physostigmine were slightly reduced but the tyramine responses were unchanged.4. Treatment with 6-OHDA at birth caused an almost complete and long-lasting noradrenaline depletion in the heart, spleen, salivary glands and ileum but only a partial depletion in the mesentery from 10-week-old rats. These low noradrenaline levels showed no recovery in rats up to an age of 4 months. The tyrosine hydroxylase activity in both the cervical and stellate ganglia from 10-week-old rats was markedly reduced by treatment with 6-OHDA after birth.5. Injections of 6-OHDA after birth produce an almost complete and permanent sympathectomy of various adrenergically innervated organs in the rat. The vascular system represents a major exception, exhibiting a surprisingly high resistance to this type of chemical adrenergic denervation.     

The effect of cyclic AMP elevating agents on bradykinin- and carbachol-induced signal transduction in canine cultured tracheal smooth muscle cells.

1. The effects of the beta 2-adrenoceptor agonist, procaterol, on sympathetic neuroeffector transmission were studied in the pithed adrenal demedullated rat to determine if generation of angiotensin II was involved in its effect. Pressor responses were elicited by either electrical stimulation (20 V, 2 Hz) of the entire spinal sympathetic outflow or methoxamine (0.1 mg kg-1, i.v.). 2. Sodium nitroprusside (3 and 5 micrograms kg-1 min-1, i.v.) produced hypotension and the pressor responses to both sympathetic nerve stimulation and methoxamine were reduced. This indicates that decreasing blood pressure in pithed rats reduces pressor responses. Procaterol (10 and 30 ng kg-1 min-1, i.v.) also produced hypotension but did not alter pressor responses to sympathetic nerve stimulation. Nevertheless, procaterol (10 and 30 ng kg-1 min-1, i.v.) did reduce pressor responses to to methoxamine. Together these results suggest that procaterol may have enhanced sympathetic neurotransmitter release. This was confirmed in another series of experiments where procaterol (30 ng kg-1 min-1, i.v.) increased plasma noradrenaline levels during sympathetic nerve stimulation. 3. Captopril (5 mg kg-1, i.v.) produced hypotension and as expected reduced pressor responses to sympathetic nerve stimulation. When the hypotensive effect of captopril was abolished by concomitant vasopressin infusion (1.5-4.5 i mu kg-1 min-1, i.v.), pressor responses to sympathetic nerve stimulation were restored to pre-captopril levels. (ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibitory effects of piribedil on adrenergic neurotransmission

The effects of piribedil on responses to sympathetic stimulation were investigated in anaesthetized dogs. Piribedil (1 mg/kg i.v.) impaired the vasoconstrictor responses to lumbar sympathetic chain stimulation of the perfused hindlimb without changing the effects of noradrenaline. Piribedil (2 mg/kg i.v.) depressed the chronotropic responses to stimulation of the right anterior ansa and the inotropic response to stimulation of the left anterior ansa. Stimulation of the splanchnic nerve induced frequency dependent increases in systemic blood pressure. Piribedil antagonized this effect. Piribedil (1 mg/kg i.v.) attenuated the constrictor responses of the perfused mesenteric artery to postganglionic sympathetic stimulation and reduced the decreases in renal blood flow caused by stimulation of sympathetic renal nerves. The inhibitory effects of piribedil were preferential on responses induced by low frequency stimulation of nerves. The hypertensive, vasoconstrictor and tachycardic effects of noradrenaline and tyramine were not affected. The effects of piribedil were reversed by haloperidol (0.5 mg/kg i.v.) or pimozide (0.2 mg/kg i.v.).     

Pharmacological alterations of vagally induced tachycardia in anesthetized dogs

Frequency-dependent tachycardia was obtained during vagal stimulation in anesnthetized, atropine-treated (1 mg/kg, i.v.) dogs. Vagally induced tachycardia was enhanced in both magnitude and duration by desipramine, whereas the magntide of tachycardia in response to cardioaccelerator nerve stimulation was not markedly enhanced. Vagal tachycardia was not inhibited by guanethidine (1 mg/kg, i.v.) but was markedly reduced after ganglion blockade by chlorisondamine (2 mg/kg, i.v.) or hexamethionium (10 mg/kg, i.v.). β-Receptor blockade by 1-oxprenolol (0.25 mg/kg, i.v.) totally blockade the response. Reserpine pretreatment decreased cardiac responses to sympathetic nerve stimulation to a greater degree than to vagal stimulation. From these results, it is suggested that the vagally induced tachycardia may be explained by acetylcholine (Ach)-mediated release of catecholamine from stores other than those susceptible to sympathetic nerve stimulation and these stores may reside in chromaffin tissue.     

A comparison of the effects of 6-hydroxydopamine immunosympathectomy and reserpine on the cardiovascular reactivity in the rat

In the conscious rat, 6-hydroxydopamine, or reserpine (5 mg/kg) pretreatment produced a marked fall in the mean systolic blood pressure whilst immunosympathectomized rats had resting blood pressures just below that of control animals. In pithed preparations, 6-hydroxydopamine treatment or immunosympathectomy potentiated the pressor responses to injected noradrenaline; reserpine pretreatment did not potentiate the noradrenaline response to the same degree. Tyramine responses were abolished after 6-hydroxydopamine or reserpine pretreatment but were unaffected by immunosympathectomy. Stimulation of the sympathetic outflow by the Gillespie & Muir (1967) preparation was abolished after 6-hydroxydopamine and reserpine pretreatment, and reduced after immunosympathectomy. It is concluded that 6-hydroxydopamine produces a destruction of the sympathetic nerve endings, abolishing the physiological uptake process and, therefore, producing supersensitivity to injected noradrenaline. Immunosympathectomy, although showing a marked reduction in sympathetic nerve supply leaves a functional uptake process. Reserpine (5 mg/kg), given 6 h previously, depletes endogenous catecholamines without significantly altering the sensitivity to injected noradrenaline, the uptake process remaining functional.     

Effects on renal sympathetic axons in dog of acute 6-hydroxydopamine treatment in combination with selective neuronal uptake inhibitors.

1. In anaesthetized dogs, we have investigated the effect on renal responses to sympathetic nerve stimulation of acute treatment with the catecholaminergic neurotoxin 6-hydroxydopamine (2 mg kg-1 i.v.), administered alone or after blockade of neuronal catecholamine uptake pathways for noradrenaline (NA) or dopamine with desmethylimipramine or benztropine, respectively. 2. Under control conditions, renal nerve stimulation caused renal vasoconstriction, reduced glomerular filtration and sodium and water excretion and caused net efflux of NA and dopamine into the renal venous plasma. Two h after administration of 6-hydroxydopamine alone, there was abolition of both functional responses and catecholamine efflux during nerve stimulation. 3. In animals pretreated with desmethylimipramine (1 mg kg-1), 6-hydroxydopamine had no significant effect on functional responses to renal nerve stimulation and nerve-evoked efflux of NA was only moderately reduced. Efflux of dopamine was still markedly reduced by 6-hydroxydopamine, but more variably than occurred without desmethylimipramine treatment. 4. In animals pretreated with benztropine (0.2 mg kg-1), nerve-evoked efflux of dopamine, but not that of NA, was protected against reduction by 6-hydroxydopamine. A higher dose of benztropine (1 mg kg-1) protected efflux of both NA and dopamine against 6-hydroxydopamine. 5. We conclude that acute treatment with a low dose of 6-hydroxydopamine is an effective method of inactivating peripheral sympathetic nerves. The differential effects of desmethylimipramine and benztropine in preserving nerve-evoked efflux of NA and dopamine after 6-hydroxydopamine support the view that these catecholamines originate predominantly from different intrarenal axons. However, neither uptake blocker appears to be completely specific in its actions.     

The cardiovascular effects of apomorphine in the anaesthetized rat

In urethane-anaesthetized rats, apomorphine, 0.01–1.0 mg/kg, i.v., produced a short-lasting fall in blood pressure and, at the higher doses (0.5–1.0 mg/kg), a marked bradycardia. Pretreatment with either reserpine or 6-hydroxydopamine did not affect the magnitude of the depressor responses. Haloperidol, spiroperidol and sulpiride failed to influence the responses to apomorphine whilst transection at the midcollicular level abolished the hypotensive responses. In pithed rat preparations, small pressor responses to apomorphine were obtained; similar effects were also observed in the anaesthetized rat treated with atropine or after bilateral vagotomy. The efferent vagal discharges were markedly increased by apomorphine, 0.1–1.0 mg/kg, whilst the discharges from the splanchnic nerve were almost completely abolished at the highest dose of apomorphine (1 mg/kg). It is concluded that the depressor effect of apomorphine is central in origin and mainly due to an increased efferent activity of the vagal nerves. This effect of apomorphine is probably not mediated by central dopaminergic receptors.     

Involvement of 5-hydroxytryptamine in the central control of respiration, blood pressure and heart rate in the anaesthetized rat.

5-Hydroxytryptamine (5-HT, 1 ng-25 μg) injected into the cerebral ventricles of urethananaesthetized rats produced a rise in blood pressure, a biphasic change in heart rate and a decrease in ventilation. Responses were largest after injections into the 3rd ventricle. Lateral ventricle injections produced smaller responses while 4th ventricle injections produced the least response. The cardiovascular responses were prevented or reduced by prior intraventricular injection of bromolysergic acid diethylamide. The pressor response was not blocked by hexamethonium (10 mg/kg i.v.) and was only partly reduced by pretreatment with either 6-hydroxydopamine (3 × 100 mg/kg i.v.) or atropine methonitrate (10 mg/kg i.v.). The pressor response was prevented by spinal transection at C1 or C3 but only slightly reduced by transection at C5 or C7. In animals curarized and artificially respired with air, the blood pressure response was reduced. It is conjectured that the rise in blood pressure may involve a direct effect of hypoxia or hypercapnia resulting from a decrease in respiratory activity which is in turn mediated by a direct action of 5-HT on structures lining the 3rd ventricles. There appears to be little or no involvement of the autonomic nervous system in the response. The fall in heart rate is mediated sympathetically.     

A COMPARISON OF THE MUSCARINIC ANTAGONIST ACTIONS OF PANCURONIUM AND ALCURONIUM

• 1 In the pithed rat, muscarine (2.5–10μg/kg i.v.) normally produced bradycardias, but tachycardias were seen in the presence of pancuronium (0.1–1.0mg/kg i.v.) and alcuronium (0.1–5.0mg/kg i.v.).
• 2 The tachycardia was probably a result of muscarinic receptor stimulation, because it was antagonized by atropine (10μg/kg i.v.) and pirenzepine (10–30μg/kg i.v.). The location of these muscarinic receptors is probably within the sympathetic ganglia since the tachycardias were inhibited by pretreatment with propranolol (1mg/kg i.v.) or reserpine (5mg/kg i.p. 24 h prior to study).
• 3 In the rat isolated atria preparation, pancuronium was 86 times more potent as an antagonist of the effects of muscarine than in the rat isolated superior cervical ganglion. The mechanism of action in both tissues may be non-competitive.
• 4 Pancuronium selectivity antagonized atrial inhibitory muscarinic responses compared to excitatory muscarinic responses in sympathetic ganglia in the rat.

     

Beta 2-adrenoceptors mediate adrenaline's facilitation of neurogenic vasoconstriction

Acute bilateral adrenal demedullation significantly reduced pressor responses in pithed spontaneously hypertensive rats. The subsequent infusion of adrenaline (50 ng/min i.v.) significantly enhanced neurogenic pressor responses without affecting those induced by noradrenaline. The adrenaline-induced enhancement of neurogenic pressor responses was unaffected by pretreatment with the beta 1-selective adrenoceptor antagonist atenolol (0.3 mg/kg i.v.), but was completely abolished by pretreatment with the beta 2-selective antagonist ICI 118551 (0.01 mg/kg i.v.). Pressor responses to noradrenaline remained unaltered.     

The central sympatho-inhibitory effect of 5,6-dihydroxy-2-dimethylaminotetralin (M7) is mediated by α2-adrenoceptors

M7 (5,6-dihydroxy-2-dimethylaminotetralin) produces in anesthetized rats a hypotensive response previously attributed to peripheral dopaminergic mechanisms. We re-examined the effects of this drug on arterial blood pressure, heart rate and sympathetic nerve activity in anesthetized rats and dogs. M7 (1–100 μg/kg i.v.) produced in the rats transient dose-dependent pressor effects, with bradycardia and sympatho-inhibition, followed by long-lasting dose-dependent hypotension, bradycardia and sympatho-inhibition. The sympatho-inhibitory and hypotensive effects were comparable in baroreceptor-denervated rats and were reversed by idazoxan (0.1 mg/kg i.v.). The sympatho-inhibitory response induced by M7 (1–100 μg/kg) was prevented by treatment with the specific α₂-adrenoceptor antagonist, 2-methoxy-idazoxan (0.03 mg/kg i.v.). This central effect of M7 was not altered by treatment with the α₁-adrenoceptor antagonist, prazosin (0.1 mg/kg i.v.) and was reduced by treatment with the α₂-adrenoceptor antagonists, yohimbine (1 mg/kg i.v.) or idazoxan (0.3 mg/kg i.v.), and the dopaminergic antagonists, haloperidol (0.5 mg/kg i.v.) or sulpiride (3 mg/kg i.v.). Bilateral microinjections of M7 (0.3–3 nmol) into the rostroventral medulla in the rat produced dose-dependent hypotension, bradycardia and sympathetic nerve inhibition which were reversed and prevented by bilateral microinjection of 2-methoxy-idazoxan (1 nmol) into the same sites. Microinjections of 2-methoxy-idazoxan into the rostroventral medulla also inhibited the central effects of M7 at 0.03 mg/kg i.v. In anesthetized dogs, M7 administered into the cisterna magna (1–10 μg/kg) reduced arterial blood pressure, heart rate and sympathetic nerve activity; these effects were reversed by administration of 2-methoxy-idazoxan (0.03 mg/kg i.v.). In conclusion, M7, a rigid catecholamine, produces a potent central sympatho-inhibitory and hypotensive effect by activation of α₂-adrenoceptors.     

Hypotensive effect in dogs and rats of intravenous injections of the alpha 1-adrenoreceptor antagonist benoxathian

The hypotensive effect of the alpha 1-adrenoreceptor antagonist benoxathian has been evaluated in rats and dogs, in comparison to that evoked by WB 4101 and prazosin. In anaesthetized dogs, i.v. injection of benoxathian (25-100 micrograms/kg), WB 4101 (5-25 micrograms/kg) and prazosin (50 micrograms/kg) produced an immediate fall in diastolic blood pressure, which reached a maximum at about 30 sec after drug administration. Whereas the hypotensive effect of prazosin persisted up to 3 hr following injection, the effect of both benoxathian and WB 4101 completely disappeared after 30-60 min. The hypotensive effect of benoxathian was dose-dependent. Pressor responses to i.v. noradrenaline (5 micrograms/kg), adrenaline (5 micrograms/kg) and phenylephrine (20 micrograms/kg) were markedly inhibited (60-75%) by benoxathian (100 micrograms/kg) whilst the pressor response to angiotensin II (0.05 micrograms/kg) was not reduced, but indeed slightly increased. The hypotensive effect of benoxathian (100 micrograms/kg) was abolished following pre-treatment with prazosin (50 micrograms/kg) or hexamethonium (1000 micrograms/kg). In anaesthetized rats similar results were obtained although recovery in blood pressure from the initial drop after i.v. injection of the drugs was slower than in dogs. Benoxathian was slightly more toxic than WB 4101 in rats. In conclusion, present findings show that benoxathian causes a profound hypotensive effect in dogs and in rats through postsynaptic alpha-adrenoreceptor blockade; however its effect, as well as that of WB 4101, is shorter lasting than that of prazosin.     

Reduction in blood pressure,sympathetic nerve discharge and centrally evoked pressor responses by methysergide in anesthetized cats

Methysergide (1 and 3 mg/kg i.v.) caused dose-dependent reductions in blood pressure and heart rate of anesthetized cats. In addition, sympathetic nerve discharges of the postganglionic renal nerve was also markedly reduced by the same doses of drug. Pressor responses to electrical stimulation of the diencephalon were inhibited by 3 mg/kg but not 1 mg/kg of methysergide. These results suggest that methysergide acts to decrease blood pressure by a centrally mediated reduction in sympathetic nervous outflow and, at higher doses, can additionally prevent pressor changes caused by electrical activation of suprabulbar central structures. These results are in agreement with previous reports that methysergide has little or no peripheral effects on the cardiovascular system.     

Excitatory and inhibitory urinary bladder reflexes induced by stimulation of cervicovaginal capsaicin-sensitive sensory fibers in rats

We have investigated the effect of intravaginal application of capsaicin on micturition reflex in female rats. Urinary bladder contractility was measured by transurethral pressure recording at isovolumetric and subthreshold conditions in anaesthetized rats. The intravaginal application of capsaicin (15 mug/50 mul rat) induced reproducible bladder phasic contractions, without desensitization upon repeated applications, that were blocked by intravenous atropine (1 mg/kg) or hexamethonium (5 mg/kg) and prevented by removal of paracervical ganglia or systemic capsaicin pretreatment (125 mg/kg, s.c.). The inhibition of sympathetic transmission by guanethidine (30 mg/kg, s.c.) produced significant increase of the bladder reflex contractions activated by intravaginal capsaicin. Intravenous administration of the TRPV1 antagonist, capsazepine (3 mg/kg), significantly reduced the excitatory reflex response to capsaicin. Intravaginal administration of capsaicin (15 mug/50 mul), during distension-induced reflex bladder contractions, produced a transient block of reflexes, unaffected by guanethidine pretreatment. In conclusion, the stimulation of capsaicin-sensitive sensory nerve endings in the rat cervix-vagina induced a dual excitatory or inhibitory bladder response in anaesthetized female rats depending on the degree of bladder distension.     

Effect of clonidine and chlorpromazine on centrally evoked electrodermal responses and their interaction with yohimbine

Both clonidine and chlorpromazine reduced the amplitude of electrodermal responses (EDR) evoked by stimulation of the hypothalamus at a constant submaximal frequency (10–16 Hz). The ED₅₀ for clonidine was approximately 5 μg/kg and that for chlorpromazine was about 1 mg/kg. Yohimbine pretreatment (0.5 mg/kg, i.v.) antagonized the effects of clonidine but did not alter the effectiveness of clorpromazine in inhibiting these responses. Yohimbine alone was without effect on these sympathetic-cholinergic responses. These results suggest that clonidine and chlorpromazine depress central sympathetic reactivity by different mechanisms.     

FRUSEMIDE INHIBITION OF SYMPATHETIC VASOCONSTRICTION IN THE RAT IN SITU BLOOD PERFUSED MESENTERY

Mesenteric perfusion pressure was measured in the in situ blood-perfused mesentery of anaesthetized rats. Increases in perfusion pressure were produced by mesenteric periarterial electrical stimulation at 3, 6 and 10 Hz before and after the administration of frusemide 5 mg/kg intravenously (i.v.) or vehicle. Loss of volume due to diuresis was prevented by replacement with intravenous saline. Frusemide did not cause any changes in blood pressure or baseline perfusion pressure. Responses to electrical stimulation were inhibited by frusemide (P less than 0.05) but unchanged by vehicle administration. Acute bilateral nephrectomy or treatment with indomethacin (2 mg/kg i.v.) prevented the inhibitory effect of frusemide on responses to sympathetic nerve stimulation. Responses to sympathetic nerve stimulation were potentiated by an infusion of angiotensin II (12 ng/min) into the mesenteric artery. This infusion did not alter either blood pressure or baseline perfusion pressure. Administration of frusemide 5 mg/kg i.v. attenuated the potentiating effect of angiotensin II on vasoconstrictor responses to electrical nerve stimulation. Frusemide may lead to the release of a prostanoid or prostanoid precursor which inhibits vascular constrictor responses.     

INHIBITION OF SYMPATHETIC NEUROTRANSMISSION BY THE OPIOID δ-RECEPTOR AGONIST DAMA IN THE PITHED RAT

1. The effects of [D-Ala2,Met5]enkephalinamide (DAMA), an analogue of [Met5]-enkephalin that acts selectively on opioid receptors of the delta-subtype, were studied on pressor responses elicited by sympathetic stimulation in pithed rats. 2. Intravenous injections of bolus doses of 0.1 mg/kg and 0.3 mg/kg of DAMA did not affect either the basal blood pressure or pressor responses to noradrenaline. 3. Pressor responses elicited either by electrical stimulation of the spinal sympathetic outflow or by stimulation of sympathetic ganglion cells with the muscarinic agonist McN-A-343 were reduced by DAMA. 4. Naloxone (1 mg/kg + 0.5 mg/kg per h) had no significant effect on the basal blood pressure or on pressor responses to spinal sympathetic stimulation, but antagonised the inhibitory effect of DAMA. 5. These results indicate that activation of opioid delta-receptors on sympathetic vasomotor nerve terminals can inhibit noradrenergic neurotransmission.