Is CRF a ganglionic transmitter or modulator in the cat sudomotor pathway?

The presence of corticotrophin releasing factor (CRF)-like immunoreactivity distinguishes a subset of cat sympathetic preganglionic neurons which supplies sweat glands. It is abundant in their terminals in the stellate ganglion. We sought first to determine whether this immunoreactivity is due to true CRF, then to test whether CRF plays any role in ganglionic transmission in the cat sudomotor pathway. CRF-immunoreactive material extracted from cat stellate ganglia and hypothalamus were eluted on HPLC at equivalent retention times, slightly less than that of standard sheep CRF. In chloralose-anaesthetised cats, sheep CRF (0.13, 1.3 and 13 μg/kg, i.v.) raised plasma immunoreactive ACTH levels by between 3- and 300-fold. Submaximal stimulus trains delivered to pre- or postganglionic nerves of the right stellate ganglion evoked electrodermal response (EDR, a measure of sweat gland activity) in the right forepaw pad as well as increases in heart rate and blood pressure. Exogenous sheep CRF (dose range 130 ng/kg to 13 mg/kg) given close-arterially to the stellate ganglion in 5 chloralose-anaesthetised cats had no consistent effect on either baseline or preganglionically-evoked EDR. Given i.v. at 13 μg/kg to four further cats, sheep CRF caused no significant change in mean baseline or mean preganglionically-evoked EDP (P > 0.05; CUSUM test). Hexamethonium (10 or 30 mg/kg i.v.) abolished the EDR to preganglionic nerve stimulation (7/7 cats). Increasing preganglionic stimulus voltage, frequency and train duration failed to show any hexamethonium-resistant component of the EDR, although such effects were evident in the cardioaccelerator pathway. We conclude that cat preganglionic sudomotor neurons contain true CRF, although the cat peptide is not identical to that of the sheep. Exogenous CRF had no measurable effect on postganglionic neurons or on ganglionic transmission in the cat sudomotor pathway. Ganglionic transmission in the sudomotor pathway, unlike that to the heart, is entirely nicotinic. The function of CRF in cat sudomotor pathway remains unknown.     

Reevaluation of the Role of the Sympathetic Nervous System in Cutaneous Vasodilation during Dorsal Spinal Cord Stimulation: Are Multiple Mechanisms Active?

Objective. In addition to treatment of refractory chronic pain in patients with peripheral vascular disease, dorsal spinal cord stimulation (DCS) increases cutaneous blood flow to the extremities and may have a limb-saving effect. The purpose of this study was to examine the role of the sympathetic nervous system in the cutaneous vasodilation due to DCS. Methods. Male Sprague-Dawley rats were anesthetized with pentobarbital (60 mg/kg, i.p.). A unipolar ball electrode was placed on the left side of the exposed spinal cord at approximately the L1-L2 level. Blood flow was concurrently recorded from both hindpaw foot pads with laser Doppler flowmeters. Blood flow responses were assessed during 1 min of DCS (0.6 mA at 50 Hz, 0.2 msec pulse duration) at 10 min intervals. To determine the contribution of the sympathetic nervous system in the blood flow response to DCS, the role of ganglionic transmission, alpha-adrenergic receptors, beta-adrenergic receptors, and adrenal catecholamine secretion were investigated using adrenergic receptor antagonists. Results. Hexamethonium (10 mg/kg, i.v.), an autonomic ganglionic receptor antagonist, did not attenuate the cutaneous vasodilation during DCS. Phentolamine (3 mg/kg, i.v.), a nonselective alpha-adrenergic receptor antagonist, also did not attenuate the DCS-induced increase in peripheral cutaneous blood flow. On the other hand, prazosin (0.1 mg/kg, i.v.), a selective alpha-1-adrenergic receptor antagonist, attenuated the DCS response but this may, at least, be partly due to a vehicle effect. Propranolol (5 mg/kg, i.v.), a nonselective beta-adrenergic receptor antagonist, attenuated the DCS response while adrenal demedullation did not. Conclusion. Overall, our results show that DCS-induced vasodilation can occur through mechanisms that are independent of sympathetic outflow.     

Acetazolamide-induced vasodilation does not inhibit the visually evoked flow response

Different methods are used to assess the vasodilator ability of cerebral blood vessels; however, the exact mechanism of cerebral vasodilation, induced by different stimuli, is not entirely known. Our aim was to investigate whether the potent vasodilator agent, acetazolamide (AZ), inhibits the neurovascular coupling, which also requires vasodilation. Therefore, visually evoked flow parameters were examined by transcranial Doppler in ten healthy subjects before and after AZ administration. Pulsatility index and peak systolic flow velocity changes, evoked by visual stimulus, were recorded in the posterior cerebral arteries before and after intravenous administration of 15 mg/kg AZ. Repeated-measures ANOVA did not show significant group main effect between the visually evoked relative flow velocity time courses before and after AZ provocation (P=0.43). Visual stimulation induced significant increase of relative flow velocity and decrease of pulsatility index not only before but also at the maximal effect of AZ. These results suggest that maximal cerebral vasodilation cannot be determined by the clinically accepted dose of AZ (15 mg/kg) and prove that neurovascular coupling remains preserved despite AZ-induced vasodilation. Our observation indicates independent regulation of vasodilation during neurovascular coupling, allowing the adaptation of cerebral blood flow according to neuronal activity even if other processes require significant vasodilation.     

Sympathetic regulation of cutaneous circulation in the rat.

The purpose of the present study was to characterize, in vivo, the function and origin of peripheral alpha-adrenergic mechanisms in acral regions of the cutaneous microvasculature. Laser-Doppler flowmetry was used to continuously monitor changes in local cutaneous microvascular perfusion (CP) measured at the plantar surface of the terminal phalange in the rat. In ketamine-anesthetized rats, the intravenous administration of phentolamine (a nonselective alpha-adrenoceptor antagonist) elicited a dose-dependent (0.01-1.0 mg/kg, i.v.) increase in CP, a decrease in mean arterial pressure (MAP) and a marked reduction in cutaneous vascular resistance (CVR). These results demonstrate a high degree of endogenous alpha-adrenergic tone in the cutaneous microvasculature of the rat. In pithed rats, cutaneous vasoconstriction could be evoked by ganglionic stimulation with DMPP or by electrical stimulation of the peripheral cut end of the sciatic nerve trunk. DMPP and sciatic nerve responses were not altered by propranolol or atropine, but were inhibited by phentolamine. In addition, the effects of DMPP on CP were abolished by bilateral adrenal demedullation, but were unaltered by hindlimb denervation. These results suggest that the predominant vasoconstrictor tone in the cutaneous vasculature is mediated by a humoral action of circulating catecholamines at postjunctional alpha-adrenoceptors. The adrenal medulla appears to be the origin of this humoral tone. Postganglionic sympathetic nerves play an insignificant role in mediating cutaneous vasoconstriction elicited by ganglionic stimulation.     

Orthostatic challenge does not alter skin sympathetic nerve activity in heat-stressed humans

Perturbations that load or unload baroreceptors do not alter skin sympathetic nerve activity (SSNA) in normothermic individuals. However, in pronounced heat-stressed individuals, when a significant component of the SSNA signal is sudomotor and possibly vasodilator in origin, the effects of baroreceptor unloading via an orthostatic stress on SSNA remain unclear. The purpose of the present study was to test the hypothesis that low and moderate levels of orthostatic stress via lower body negative pressure (LBNP) alter SSNA in pronounced heat-stressed individuals. In both normothermic and heat-stressed conditions, progressive LBNP at -3, -6, -9, -12, -15, -18, -21 and -40 mm Hg were applied to 11 subjects for 2 min per stage. Whole-body heating increased sublingual temperature by 0.7+/-0.1 degrees C, heart rate by 28+/-2.1 bpm, SSNA by 259+/-76 %, forearm skin blood flow by 631+/-142% and forearm sweat rate to 0.68+/-0.14 mg/cm(2)/min (all p<0.005), but did not change mean arterial blood pressure (MAP) (p>0.05). LBNP did not change total SSNA in normothermic or heat-stressed conditions (both p>0.05), although skin blood flow and sweat rate decreased during moderate levels of LBNP while heat stressed. These data suggest that in pronounced heat-stressed individuals, when a significant component of the SSNA signal contains sudomotor and possibly cutaneous active vasodilator activities, low and moderate levels of baroreceptor unloading via LBNP do not alter total SSNA. This observation, coupled with reductions in skin blood flow and sweating during moderate levels of LBNP, suggests that integrated SSNA should not be used as an indicator of baroreflex modulation of the cutaneous vasculature or sweat rate in heat-stressed subjects.     

Lack of sympathetic and cholinergic influences on cerebral vasodilation caused by sciatic nerve stimulation in the rat

We studied the influences of sympathetic and cholinergic mechanisms on pial arteriolar responses during cortical activation in the rat. Adult male Sprague-Dawley rats were anesthetized with alpha-chloralose and urethane and mechanically ventilated. Pial arterioles on the somatosensory cortex were visualized on a video monitor through a closed cranial window. Changes in arteriolar diameter induced by sciatic nerve stimulation (0.2 V, 5 Hz, 5 ms, for 20 s) were measured before and after (a) ipsilateral superior cervical ganglionectomy (n = 5), (b) intravenous (0.5 mg/kg) administration and topical (10(-5) M) application of atropine (n = 5), and (c) lesion of the nucleus basalis magnocellularis (the major source of intracerebral acetylcholine neurons, n = 7). Unilateral nucleus basalis magnocellularis lesions were performed stereotactically by injection of ibotenic acid (25 nmol/microliter). Sensory cortex cholinergic denervation was confirmed histologically. These treatments had no significant effect on arteriolar responses to sciatic nerve stimulation. Thus, the present results suggest that neither sympathetic nor cholinergic mechanisms play a significant role in somatosensory evoked cerebral vasodilation.     

Differentiation of neurogenic vasoconstrictor responses in skin and skeletal muscle of dog hindlimb

Femoral blood flow was measured electromagnetically in chloralose-anaesthetised dogs pretreated with atropine and pancuronium, during preganglionic stimulation of the ipsilateral lumbar sympathetic chain. Circulation to the paw pads was occluded with a ligature. Trains of 10 stimuli at frequencies of 4 or 40 Hz elicited vasoconstrictor responses, the recovery phases of which were prolonged during temporary occlusion of the circulation to the leg below the knee, and shortened in the presence of low doses of the ganglion blocking drug hexamethonium (0.5-3 mg/kg i.v.). Numerical summation of the responses persisting after 2 mg/kg hexamethonium and those obtained during lower limb occlusion produced curves that closely matched control responses in timecourse and amplitude. It is suggested that skin and muscle resistance vessels in the hindlimb receive their primary vasoconstrictor nerve supply via peripheral pathways that can be distinguished by the sensitivity to hexamethonium of their ganglionic synapses, and that the timecourse of constrictor responses in skeletal muscle is longer than that in skin.     

Selective excitation of parasympathetic nerve fibers to elicit the vasodilatation in cat lip.

Electrical stimulation of the tongue and the proximal cut end of the lingual nerve caused a blood flow to increase in a stimulus-intensity dependent manner in the ipsilateral lower lip of the cats. Pretreatment with hexamethonium (an autonomic ganglionic blocker, 1.0 mg/kg) abolished the vasodilator response, while atropine, phentolamine, propranolol and tripelennamine had no effect on these vasoresponses. Ipsilateral sections of either the glossopharyngeal nerve root, inferior alveolar nerve or mental nerve at the main mental foramen, but not at the posterior mental foramen, abolished the vasodilator response caused by electrical stimulation of the tongue and the lingual nerve. Electrical stimulation of the distal cut ends of the glossopharyngeal nerve root and inferior alveolar nerve caused the vasodilator and vasoconstrictor responses, whereas stimulation of the tongue and the proximal cut ends of the lingual nerve did not elicit the vasoconstrictor response. These results suggest that reflex vasodilatation in the cat mandibular division is exclusively mediated via activation of the parasympathetic nerve fibers, and that selective excitation of the parasympathetic nerve fibers in the oral area is possible.     

Evidence for involvement of endogenous acetylcholine in emotional-aversive response in the cat

1. The purpose of the present study was to provide evidence for involvement of endogenous acetylcholine in naturally as well as pharmacologically induced emotional behaviour in the cat. 2. Emotional-aversive responses of 10 cats were naturally evoked by presentation of a dog or the responses were pharmacologically induced by intracerebral injections of cholinomimetics. 3. Naturally evoked emotional behaviour was abolished by i.p. pretreatment with atropine sulfate (1 mg/kg), but not by atropine methyl nitrate, or it was significantly decreased by bilateral intracerebral injection of atropine sulfate (5 micrograms/microliter). 4. On the other hand, intracerebral injections of physostigmine (100 micrograms/microliter), an acetylcholinesterase inhibitor which elevates the level of endogenous acetylcholine, induced the fully developed emotional-aversive response comparable with natural behaviour and with responses induced by carbachol (10 micrograms/microliter). 5. The results demonstrate that the endogenous acetylcholine in the basal forebrain and diencephalic areas play a role in naturally occurring emotional aversive behaviour in cats.     

Spinal segmental sympathetic outflow to cervical sympathetic trunk, vertebral nerve, inferior cardiac nerve and sympathetic fibres in the thoracic vagus

The spinal segmental localization of preganglionic neurons which convey activity to the sympathetic nerves, i.e. vertebral nerve, right inferior cardiac nerve, sympathetic fibres in the thoracic vagus and cervical sympathetic trunk, was determined on the right side in chloralose anaesthetized cats. For that purpose the upper thoracic white rami were electrically stimulated with a single pulse, suprathreshold for B and C fibres, and the evoked responses were recorded in the sympathetic nerves. The relative preganglionic input from each segment of the spinal cord to the four sympathetic nerves was determined from the size of the evoked responses. It was found that each sympathetic nerve receives a maximum preganglionic input from one segment of the spinal cord (dominant segment) and that the preganglionic input gradually decreased from neighbouring segments. The spinal segmental preganglionic outflow to the cervical sympathetic trunk, thoracic vagus, right inferior cardiac nerve and vertebral nerve gradually shifted from the most rostral to the most caudal spinal cord segments. In some cases, a marked postganglionic component was found in the cervical sympathetic trunk. It was evoked by preganglionic input from the same spinal cord segments which transmitted activity to the vertebral nerve. These results indicate that there is a fixed relation between the spinal segmental localization of preganglionic neurons and the branch of the stellate ganglion receiving the input from these neurons.     

Transmission of impulses from pre- to postganglionic vasoconstrictor and sudomotor neurons

Transmission of impulses of pre- to postganglionic neurons supplying skeletal muscle and skin of the cat's hindlimb and tail was investigated. The objective of the study was to determine whether these postganglionic neurons can be influenced from the preganglionic side by non-nicotinic synaptic mechanisms in the lumbar sympathetic chain ganglia. The activity of the postganglionic neurons was recorded from their axons being isolated from peripheral skin and muscle nerves. (1) Vasoconstrictor neurons can be activated by muscarinic action of released acetylcholine and by a non-cholinergic synaptic mechanism. This type of non-nicotinic excitation of postganglionic vasoconstrictor neurons requires the activation of thin, probably unmyelinated preganglionic axons and considerable summation. Postganglionic sudomotor and pilomotor neurons cannot be activated in this way. (2) Ongoing activity in postganglionic vasoconstrictor neurons, but not in sudomotor neurons, can be enhanced for up to 60 min by brief trains of stimuli applied to the preganglionic site. Also this enhancement requires the activation of thin preganglionic axons. (3) Stimulation of thin preganglionic axons leads to an activation of muscle vasoconstrictor neurons via non-nicotinic synaptic mechanisms in the ganglia after complete block of nicotine transmission. (4) Postganglionic vasoconstrictor neurons and sudomotor neurons may be inhibited by a catecholaminergic autogenic mechanism in the ganglia. (5) The results indicate that integration may take place in the sympathetic chain ganglia by other than divergent and convergent processes. In this integration muscarinic actions of released acetylcholine and non-cholinergic synaptic mechanisms may be involved.     

Intersegmental connections and interactions of myelinated somatic and visceral afferents with sympathetic preganglionic neurons in the unanesthetized spinal cat

The aim of this study was to obtain a measure of the interactions through exclusively spinal circuits, of myelinated afferents with sympathetic preganglionic neurons. Experiments were performed on 16 unanesthetized cats rendered insensitive by bilateral vertebral and carotid occlusion, whose spinal cords had been transected at C1 6-12 h before recording. The evoked responses of 68 tonically active sympathetic preganglionic neurons were recorded from filaments dissected from the cervical sympathetic trunk. Excitation, inhibition and excitation-inhibition sequences were evoked by electrical stimulation of radial, femoral and pelvic nerve afferents. Inhibition was most often observed during pelvic nerve stimulation. Ninety percent of the sympathetic preganglionic neurons tested responded to radial, 77% to femoral and 85% to pelvic nerve stimulation. These differences in percentage of units responding to the three nerves were statistically insignificant. Thus, in the acute spinal cat, the fraction of tonically active sympathetic preganglionic neurons whose activity can be influenced by myelinated afferents is independent of the length of the intraspinal pathway which conveys the input. A main difference between the long pathway (mediating the responses to femoral or pelvic nerve) and the short pathway (mediating the responses to radial nerve) seems to be the efficacy of their connections. While single shocks reliably evoked responses from the radial nerve, trains (200 Hz, 20 msec) were usually necessary to elicit responses from femoral or pelvic nerve, indicating a requirement for summation in the long pathway.     

Pancreatic vasoconstrictor responses are regulated by neurons in the rostral ventrolateral medulla

The pancreas receives sympathetic input which arises from several premotor cell groups in the CNS including the rostral ventrolateral medulla (RVLM). In this study, we examined the influence of electrical stimulation of the RVLM on pancreatic blood flow measured by laser Doppler flowmetry and gastric blood flow measured by ultrasonic Doppler flowmetry in halothane-anesthetized rats. The laser Doppler flow measurement technique was validated by demonstration that pancreatic conductance was reduced by systemic administration of the vasoconstrictor phenylephrine and increased by the vasodilator sodium nitroprusside. Sympathetic vasomotor withdrawal induced by either administration of phenylbiguanide (2 and 10 microg/kg, i.v.) or electrical stimulation of the central end of the cervical vagal trunk (5 Hz, 2 ms, 50-150 microA) produced depressor responses and increases in pancreatic and gastric vascular conductance. Electrical stimulation of the RVLM (50 Hz, 0.5 ms, 25-75 microA) produced pressor and tachycardic responses accompanied by decreases in pancreatic and gastric vascular conductance. All responses to RVLM stimulation were abolished by blockade of ganglionic neurotransmission (hexamethonium bromide, 20 mg/kg, i.v.). These data suggest that RVLM presympathetic vasomotor neurons are a primary source of tonic sympathetic vasomotor drive to the pancreatic and gastric vasculature.     

Occurrence of the spinal reflex due to skin pressure in sudomotor and cutaneous vasoconstrictor nerve system of humans

The effects of skin pressure applied to one side of the waist on sudomotor and vasoconstrictor nerve activity were compared with the effects on sweating and cutaneous blood flow in humans. The sweat rate and cutaneous blood flow were measured on left and right dorsal feet. Skin sympathetic nerve activity (SSNA) was recorded by microneurography from a microelectrode inserted in left and right peroneal nerves. Skin pressure was applied in a supine position to the area over the left or right anterior superior iliac spine under warm (T(a): 30-36 degrees C) and cool (T(a): 19-23 degrees C) conditions. Sudomotor and vasoconstrictor bursts were identified for quantitative analysis. The skin pressure increased the contralateral/ipsilateral ratio of the sweat rate. It also increased the contralateral/ipsilateral ratio of the cutaneous blood flow and the contralateral/ipsilateral ratio of the sudomotor burst amplitude. However, skin pressure did not induce any significant changes in the contralateral/ipsilateral ratio of the vasoconstrictor burst amplitude. The results indicate that an asymmetrical reflex effect of skin pressure on vasoconstrictor nerve activity was absent, suggesting that, whereas the ipsilateral suppression of sweating elicited by skin pressure was mediated by the sudomotor nerve system, the ipsilateral suppression of cutaneous blood flow was not mediated by the vasoconstrictor nerve system. Thus, the occurrence of the spinal reflex due to skin pressure is not uniform between the sudomotor and the vasoconstrictor nerve systems, which represent different organizations at the level of spinal cord.     

Purinergic mechanisms of the nucleus of the solitary tract and neural cardiovascular control

OBJECTIVES: This review addresses the role of central purinergic receptors in the operation of the cardiovascular reflexes. METHODS: Potential physiological role of purinergic receptors operating in the nucleus of the solitary tract (NTS) was assessed via comparison of the regional patterns of hemodynamic and sympathetic responses evoked by selective stimulation/inhibition of NTS purinergic receptor subtypes, with the patterns evoked by stimulation and unloading of arterial baroreceptors, and other known patterns of autonomic responses. The effects of sino-aortic denervation plus vagotomy and ionotropic glutamatergic blockade of NTS mechanisms on the patterns of the responses were also considered. RESULTS: Selective stimulation of NTS A1 receptors with CPA evoked a pattern of regional autonomic responses consistent with inhibition of baroreflex mechanisms and facilitation/ disinhibition of chemoreflex mechanisms. Selective stimulation of NTS A(2a) receptors with CGS 21680-evoked pattern of the responses different than that evoked by stimulation of baroreflex afferents what remains in contrast to previous reports suggesting that NTS A2a receptors facilitate baroreflex transmission. The pattern of the responses was similar to that observed during hypotensive hemorrhage. Preferential, b -adrenergic iliac vasodilation evoked by stimulation of adenosine A2a receptors and preferential activation of sympathetic output to the adrenal medulla by both adenosine A1 and A2a receptors are consistent with contribution of these receptors to the defense response, stress and exercise. These observations support previous findings that NTS A1 receptors contribute to the hypothalamic defense response. The effects of stimulation and blockade of NTS P2x receptors with alpha, beta-methylene ATP and suramin, respectively, suggested that neuronally-released ATP operating via P2x receptors may be a crucial co-transmitter with glutamate in mediating baroreflex responses. DISCUSSION: The above observations strongly suggest that purinergic receptor subtypes operating in NTS circuitry are linked to specific afferent and descending mechanisms primarily integrated in the NTS.     

Medial prefrontal cortex acetylcholine injection-induced hypotension: the role of hindlimb vasodilation

The injection of acetylcholine (ACh) into the cingulate region of the medial prefrontal cortex (MPFC) causes a marked fall in arterial blood pressure which is not accompanied by changes in heart rate. The purpose of the present study was to investigate the hemodynamic basis for this stimulus-induced hypotension in Sprague-Dawley rats. The study was designed to determine whether a change in the vascular resistance of hindlimb, renal or mesenteric vascular beds contributes to the fall in arterial pressure in response to ACh injection into the cingulate cortex. Miniature pulsed-Doppler flow probes were used to measure changes in regional blood flow and vascular resistance. The results indicated that the hypotensive response was largely due to a consistent and marked vasodilation in the hindlimb vascular bed. On this basis, an additional experiment was then undertaken to determine the mechanisms that contribute to hindlimb vasodilation. The effect of interrupting the autonomic innervation of one leg on the hindlimb vasodilator response was tested. Unilateral transection of the lumbar sympathetic chain attenuated the cingulate ACh-induced vasodilation in the ipsilateral, but not in the contralateral hindlimb. These results suggest that the hypotensive response to cingulate cortex-ACh injection is caused by skeletal muscle vasodilation mediated by a sympathetic chain-related vasodilator system.     

Lithium enhancement of central 5-HT transmission induced by 5-HT precursors

The effects of acute and chronic lithium chloride administration on synaptic transmission between bulbospinal norepinephrine (NE) or 5-hydroxy-tryptamine (5-HT) pathways and sympathetic preganglionic neurons were tested in unanesthetized, spinal cats. Discharges recorded from sympathetic preganglionic white rami were evoked by stimulation of spinal reflex pathways or descending excitatory pathways in the cervical spinal cord. Acute lithium administration (2 meq/kg) produced insignificant depression of the reflex pathway but markedly depressed transmission through the intraspinal pathway, an effect that was prevented by depletion or blockage of 5-HT. These observations and the failure of lithium to alter the typical effects of L-dopa on both pathways indicate that lithium does not affect transmission through the excitatory NE pathway. L-Tryptophan (1,0 mg/kg) alone produced little or no depression of either pathway, but 3--4 hr after lithium, this dose of L-tryptophan gradually depressed transmission through both pathways by about 20%. After chronic lithium pretreatment (1 meq/kg twice a day for 3 days), L-tryptophan rapidly depressed transmission through spinal reflex and intraspinal pathways by 40% and 50% respectively. Chronic lithium pretreatment also more than doubled the depression of transmission through both pathways produced by 30 mg/kg of 5-HTP. The average of plasma lithium levels 8--10 hr after the last chronic dose was 1.5 meq/liter. These results support the proposal that lithium increases the uptake of L-tryptophan and 5-HTP by central 5-HT terminals and thereby enhances 5-HT synthesis which is reflected in increased transmission at central 5-HT synapses.     

Adaptation of the hypothalamic blood flow to chronic nitric oxide deficiency is independent of vasodilator prostanoids

The aim of our study was to investigate the adaptation of the hypothalamic circulation to chronic nitric oxide (NO) deficiency in rats. Hypothalamic blood flow (HBF) remained unaltered during chronic oral administration of the NO synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME, 1 mg/ml drinking water) although acute NOS blockade by intravenous l-NAME injection (50 mg/kg) induced a dramatic HBF decrease. In chronically NOS blocked animals, however, acute l-NAME administration failed to influence the HBF. Reversal of chronic NOS blockade by intravenous l-arginine infusion evoked significant hypothalamic hyperemia suggesting the appearance of a compensatory vasodilator mechanism in the absence of NO. In order to clarify the potential involvement of vasodilator prostanoids in this adaptation, cyclooxygenase (COX) mRNA and protein levels were determined in the hypothalamus, but none of the known isoenzymes (COX-1, COX-2, COX-3) showed upregulation after chronic NOS blockade. Furthermore, levels of vasodilator prostanoid (PGI(2), PGE(2) and PGD(2)) metabolites were also not elevated. Interestingly, however, hypothalamic levels of vasoconstrictor prostanoids (TXA(2) and PGF(2alpha)) decreased after chronic NOS blockade. COX inhibition by indomethacin but not by diclofenac decreased the HBF in control animals. However, neither indomethacin nor diclofenac induced an altered HBF-response after chronic l-NAME treatment. Although urinary excretion of PGI(2) and PGE(2) metabolites markedly increased during chronic NOS blockade, indicating COX activation in the systemic circulation, we conclude that the adaptation of the hypothalamic circulation to the reduction of NO synthesis is independent of vasodilator prostanoids. Reduced release of vasoconstrictor prostanoids, however, may contribute to the normalization of HBF after chronic loss of NO.     

Spinal segmental preganglionic outflow to cervical sympathetic trunk and postganglionic cardiac sympathetic nerves

The aim of this study was to verify in which spinal cord segments the preganglionic neurones projecting to the cervical sympathetic trunk or converging onto the somata of the postganglionic cardiac sympathetic neurones are located in cats. The thoracic white rami T1 to T5 were electrically stimulated and the evoked responses were recorded in the cervical sympathetic trunks and postganglionic cardiac nerves. The responses were mostly evoked by electrical stimulation of group B preganglionic fibres. The maximum amplitude of evoked responses in the cervical sympathetic trunk was obtained when the T2 white ramus was stimulated and decreased gradually when followed by the stimulation of T1, T3, T4 and T5 white rami. In most cases the maximum amplitude of evoked responses in the left inferior cardiac nerve, right inferior cardiac nerve and left middle cardiac nerve was obtained when the T3 white ramus was stimulated. The size of the responses decreased when more cranial and caudal white rami were stimulated. It was found that the somata of the postganglionic neurones of the right and left inferior cardiac nerves were placed in the right and left stellate ganglion, respectively. Somata of the postganglionic neurones with axons in the left middle cardiac nerve were mainly located in the left middle cervical ganglion and some in the left stellate ganglion.     

Vascular abnormalities in acute reflex sympathetic dystrophy (CRPS I): complete inhibition of sympathetic nerve activity with recovery.

BACKGROUND: Reflex sympathetic dystrophy/complex regional pain syndrome type I (RSD/CRPS I) is a painful neuropathic disorder that may develop as a disproportionate consequence of a trauma affecting the limbs without overt nerve injury. Clinical features are spontaneous pain, hyperalgesia, impairment of motor function, swelling, changes in sweating, and vascular abnormalities. OBJECTIVE: To investigate pathophysiological mechanisms of vascular abnormalities in RSD/CRPS I. DESIGN: Case study. SETTING: Autonomic test laboratory at a university hospital. PARTICIPANTS: A patient with an early stage of RSD/ CRPS I of the upper limb and 2 healthy control subjects. INTERVENTIONS: Cutaneous sympathetic vasoconstrictor innervation was assessed by measuring cutaneous blood flow (laser Doppler flowmetry) and skin temperature (infrared thermometry). To quantify sympathetic vasoconstrictor function, phasic (induced by deep inspiration) and tonic (induced by controlled thermoregulation) sympathetic reflexes were analyzed. Venous norepinephrine levels were determined bilaterally. The same tests were performed in the controls after induction of cutaneous antidromic vasodilation produced by histamine dihydrochloride application. MAIN OUTCOME MEASURE: Sympathetic cutaneous vasoconstrictor function in RSD/CRPS 1. RESULTS: Two weeks after the onset of RSD/CRPS I, skin temperature on the affected side was higher (close to core body temperature) than on the contralateral side at room temperature and during controlled thermoregulation, indicating maximal vasodilation. Phasic and tonic stimulation of cutaneous vasoconstrictor neurons did not induce a decrease of skin blood flow or temperature on the affected side but were normal on the contralateral side. Venous norepinephrine levels were lower on the affected side. Parallel to clinical improvement, loss of vasoconstrictor function completely recovered within weeks. Results of investigations in healthy subjects ruled out the possibility that antidromic vasodilation caused by activation of nociceptive afferents is responsible for the complete depression of sympathetic vasoconstrictor reflexes. CONCLUSIONS: Demonstrated for the first time is a complete functional loss of cutaneous sympathetic vasoconstrictor activity in an early stage of RSD/CRPS I with recovery. The origin of this autonomic dysfunction is in the central nervous system.