Enhanced neurally evoked responses and inhibition of norepinephrine reuptake in rat mesenteric arteries after spinal transection

2006 ◽  
Vol 290 (1) ◽  
pp. H398-H405 ◽  
Author(s):  
James A. Brock ◽  
Melanie Yeoh ◽  
Elspeth M. McLachlan
Keyword(s):  
Mesenteric Arteries ◽  
Autonomic Dysreflexia ◽  
Neuronal Uptake ◽  
Spinal Transection ◽  
Adrenoceptor Antagonist ◽  
Thoracic Spinal ◽  
Adrenoceptor Agonist ◽  
High K ◽  
The Difference ◽  
Evoked Contractions

In patients with high thoracic spinal lesions that remove most of the central drive to splanchnic preganglionic neurons, visceral or nociceptive stimuli below the lesion can provoke large increases in blood pressure (autonomic dysreflexia). We have examined the effects of T4 spinal transection on isometric contractions of mesenteric arteries isolated from spinalized rats. Nerve-evoked contractions involved synergistic roles for norepinephrine and ATP. At 7 wk after spinal transection, responses to perivascular stimulation at 1–5 Hz were enhanced fivefold, whereas the α1-adrenoceptor antagonist prazosin (10 nM) produced a twofold larger reduction in contraction (to 20 pulses at 10 Hz) than in unoperated controls. In contrast, the reduction in nerve-evoked contractions by the P2-purinoceptor antagonist suramin (0.1 mM) and the responses to the P2-purinoceptor agonist α,β-methylene ATP or to high K+ concentration did not greatly differ between groups, indicating that arteries from spinalized rats were not generally hyperreactive. Sensitivity to the α1-adrenoceptor agonist phenylephrine was enhanced in arteries from spinalized rats, and the difference from controls was abolished by the norepinephrine uptake blocker desmethylimipramine. Sensitivity to the α1-adrenoceptor agonist methoxamine, which is not a substrate for the neuronal norepinephrine transporter, was similar among the groups. Thus the increased neurally evoked response after spinal transection appeared to be due to a reduction in neuronal uptake of released norepinephrine, a mechanism that did not explain the enhanced response of tail arteries after spinal transection that we previously reported. The findings provide further support for potentiated neurovascular responses contributing to the genesis of autonomic dysreflexia.

Slow and incomplete sympathetic reinnervation of rat tail artery restores the amplitude of nerve-evoked contractions provided a perivascular plexus is present

2011 ◽  
Vol 300 (2) ◽  
pp. H541-H554 ◽  
Author(s):  
Diana Tripovic ◽  
Svetlana Pianova ◽  
Elspeth M. McLachlan ◽  
James A. Brock
Keyword(s):  
Rat Tail Artery ◽  
Adult Rats ◽  
Tail Artery ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Perivascular Plexus ◽  
Evoked Contractions ◽  
Comparable Amplitude ◽  
Rat Tail

We have investigated the recovery of sympathetic control following reinnervation of denervated rat tail arteries by relating the reappearance of noradrenergic terminals to the amplitude of nerve-evoked contractions of isometrically mounted artery segments in vitro. We have also assessed reactivity to vasoconstrictor agonists. Freezing the collector nerves near the base of the tail in adult rats denervated the artery from ∼40 mm along the tail. Restoration of the perivascular plexus declined along the length of the tail, remaining incomplete for >6 mo. After 4 mo, nerve-evoked contractions were prolonged but of comparable amplitude to control at ∼60 mm along the tail; they were smaller at ∼110 mm. At ∼60 mm, facilitation of contractions to short trains of stimuli by the norepinephrine transporter blocker, desmethylimipramine, and by the α2-adrenoceptor antagonist, idazoxan, was reduced in reinnervated arteries. Blockade of nerve-evoked contractions by the α1-adrenoceptor antagonist, prazosin, was less and by idazoxan greater than control after 8 wk but similar to control after 16 wk. Sensitivity of reinnervated arteries to the α1-adrenoceptor agonist, phenylephrine, was raised in the absence but not in the presence of desmethylimipramine. Sensitivity to the α2-adrenoceptor agonist, clonidine, was maintained in 16-wk reinnervated arteries when it had declined in controls. Thus regenerating sympathetic axons have a limited capacity to reinnervate the rat tail artery, but nerve-evoked contractions match control once a relatively sparse perivascular plexus is reestablished. Functional recovery involves prolongation of contractions and deficits in both clearance of released norepinephrine and autoinhibition of norepinephrine release.

Role of endothelin in α-adrenoceptor coronary vasoconstriction

2005 ◽  
Vol 288 (4) ◽  
pp. H1937-H1942 ◽  
Author(s):  
Mark W. Gorman ◽  
Martin Farias ◽  
Keith N. Richmond ◽  
Johnathan D. Tune ◽  
Eric O. Feigl
Keyword(s):  
Oxygen Tension ◽  
Endothelin Receptor ◽  
Coronary Smooth Muscle ◽  
Coronary Vasoconstriction ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Resistance Vessels ◽  
Anesthetized Dogs ◽  
The Difference

It has been proposed that α-adrenoceptor vasoconstriction in coronary resistance vessels results not from α-adrenoceptors on coronary smooth muscle but from α-adrenoceptors on cardiac myocytes that stimulate endothelin (ET) release. The present experiments tested the hypothesis that the α-adrenoceptor-mediated coronary vasoconstriction that normally occurs during exercise is due to endothelin. In conscious dogs ( n = 10), the endothelin ETA/ETB receptor antagonist tezosentan (1 mg/kg iv) increased coronary venous oxygen tension at rest but not during treadmill exercise. This result indicates that basal endothelin levels produce a coronary vasoconstriction at rest that is not observed during the coronary vasodilation during exercise. In contrast, the α-adrenoceptor antagonist phentolamine increased coronary venous oxygen tension during exercise but not at rest. The difference between the endothelin blockade and α-adrenoceptor blockade results indicates that α-adrenoceptor coronary vasoconstriction during exercise is not due to endothelin. However, in anesthetized dogs, bolus intracoronary injections of the α-adrenoceptor agonist phenylephrine produced reductions in coronary blood flow that were partially antagonized by endothelin receptor blockade with tezosentan. These results are best explained if α-adrenoceptor-induced endothelin release requires high pharmacological concentrations of catecholamines that are not reached during exercise.

Neurogenic dilatation and constriction of rat superior mesenteric artery in vitro: mechanisms and mediators

1986 ◽  
Vol 64 (6) ◽  
pp. 729-736 ◽  
Author(s):  
M. S. Kannan ◽  
A. E. Seip
Keyword(s):  
Substance P ◽  
Sympathetic Nerve Activity ◽  
Mesenteric Arteries ◽  
Opioid Agonist ◽  
Nerve Activity ◽  
Mechanical Responses ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Voltage Dependent

In the rat superior mesenteric arteries, the mechanical responses to perivascular nerve stimulation were characterized. The predominant response was contraction mediated by the release of norepinephrine, acting postjunctionally on α1-adrenoceptors. These frequency-dependent contractions were unaffected by the α2-selective adrenoceptor antagonist yohimbine, but were markedly attenuated by clonidine, the α2-selective adrenoceptor agonist. In the presence of prazosin, the α1-selective antagonist, a significant component of the nerve-mediated contraction was still present. At the concentrations used, prazosin, yohimbine, as well as clonidine acted as competitive antagonists of response to exogenous norepinephrine. This differential inhibition of norepinephrine- and nerve-mediated responses suggested the presence of distinct postjunctional adrenoceptors. The effects of clonidine and yohimbine are interpreted to arise from prejunctional modulation of norepinephrine release. In 30 of the 100 vessels studied, there was spontaneous myogenic tone. In these arteries, field stimulation caused frequency- and voltage-dependent relaxations. These responses were neural in origin, dependent on sympathetic nerve activity, but were nonadrenergic and noncholinergic in nature. Naloxone, indomethacin, and substance P inhibited these relaxations with no significant effect on the tone. The opioid agonist, 1–13 dynorphin relaxed these vessels and only naloxone inhibited this response. The effects of these agents were selective against field-stimulated responses since they did not alter the relaxation to the nonspecific agent sodium nitroprusside. These results provide circumstantial evidence for opioid-mediated vascular relaxation that is presynaptically modulated by prostanoids and substance P.

Testosterone-augmented contractile responses to α1- and β1-adrenoceptor stimulation are associated with increased activities of RyR, SERCA, and NCX in the heart

2009 ◽  
Vol 296 (4) ◽  
pp. C766-C782 ◽  
Author(s):  
Sharon Tsang ◽  
Stanley S. C. Wong ◽  
Song Wu ◽  
Gennadi M. Kravtsov ◽  
Tak-Ming Wong
Keyword(s):  
Ventricular Myocytes ◽  
Left Ventricular ◽  
Contractile Responses ◽  
Adrenoceptor Antagonist ◽  
Cardiac Contractile ◽  
Plasmic Reticulum ◽  
Adrenoceptor Agonist ◽  
Intracellular Ca ◽  
Developed Pressure ◽  
Stimulation Of

We hypothesized that testosterone at physiological levels enhances cardiac contractile responses to stimulation of both α1- and β1-adrenoceptors by increasing Ca2+ release from the sarcoplasmic reticulum (SR) and speedier removal of Ca2+ from cytosol via Ca2+-regulatory proteins. We first determined the left ventricular developed pressure, velocity of contraction and relaxation, and heart rate in perfused hearts isolated from control rats, orchiectomized rats, and orchiectomized rats without and with testosterone replacement (200 μg/100 g body wt) in the presence of norepinephrine (10−7 M), the α1-adrenoceptor agonist phenylephrine (10−6 M), or the nonselective β-adrenoceptor agonist isoprenaline (10−7 M) in the presence of 5 × 10−7 M ICI-118,551, a β2-adrenoceptor antagonist. Next, we determined the amplitudes of intracellular Ca2+ concentration transients induced by electrical stimulation or caffeine, which represent, respectively, Ca2+ release via the ryanodine receptor (RyR) or releasable Ca2+ in the SR, in ventricular myocytes isolated from the three groups of rats. We also measured 45Ca2+ release via the RyR. We then determined the time to 50% decay of both transients, which represents, respectively, Ca2+ reuptake by sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and removal via the sarcolemmal Na+/Ca2+ exchanger (NCX). We correlated Ca2+ removal from the cytosol with activities of SERCA and its regulator phospholamban as well as NCX. The results showed that testosterone at physiological levels enhanced positive inotropic and lusitropic responses to stimulation of α1- and β1-adrenoceptors via the androgen receptor. The increased contractility and speedier relaxation were associated with increased Ca2+ release via the RyR and faster Ca2+ removal out of the cytosol via SERCA and NCX.

Effects of α-adrenoceptor agonists and antagonists on thyroid hormone secretion

1985 ◽  
Vol 108 (2) ◽  
pp. 184-191 ◽  
Author(s):  
Bo Ahrén
Keyword(s):  
Thyroid Hormone ◽  
Dose Level ◽  
Hormone Secretion ◽  
High Dose ◽  
Inhibitory Effects ◽  
High Dose Level ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Adrenoceptor Agonists

Abstract. The effects of various α-adrenoceptor agonists and antagonists on blood radioiodine levels were studied in mice pre-treated with 125I and thyroxine. The non-selective α-adrenoceptor agonist noradrenaline and the selective α1-adrenoceptor agonist phenylephrine both enhanced blood radioiodine levels. Noradrenaline was more potent than phenylephrine. Contrary, the selective α2-adrenoceptor agonist clonidine depressed basal levels of blood radioiodine. The non-selective α-adrenoceptor antagonist phentolamine and the selective α1-adrenoceptor antagonist prazosin both inhibited the noradrenaline-induced elevation of radioiodine levels, whereas the α2-adrenoceptor antagonist yohimbine had no such effect, except at a high dose level. All three α-adrenoceptor agonists, noradrenaline, phenylephrine and clonidine, inhibited the radioiodine response to TSH. In addition, TSH-induced increase in radioiodine levels was inhibited by prazosin, whereas yohimbine had no effect. Phentolamine inhibited the radioiodine response to TSH when given 2 h prior to TSH, whereas when given 15 min prior to TSH the response to TSH was potentiated by Phentolamine. It is concluded, that under in vivo conditions in the mouse, α1-adrenoceptor activation stimulates basal thyroid hormone secretion and inhibits TSH-induced thyroid hormone secretion. Further, α2-adrenoceptor activation inhibits basal thyroid hormone secretion. In addition, TSH-induced thyroid hormone secretion is inhibited by α1-adrenoceptor antagonism. Thus, α-adrenoceptors induce both stimulatory and inhibitory effects of thyroid function.

Drastic Decrease in Isoflurane Minimum Alveolar Concentration and Limb Movement Forces after Thoracic Spinal Cooling and Chronic Spinal Transection in Rats

2005 ◽  
Vol 102 (3) ◽  
pp. 624-632 ◽  
Author(s):  
Steven L. Jinks ◽  
Carmen L. Dominguez ◽  
Joseph F. Antognini
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Minimum Alveolar Concentration ◽  
Tail Flick ◽  
Noxious Stimulation ◽  
Partial Recovery ◽  
Spinal Transection ◽  
Thoracic Spinal ◽  
Cord Injury ◽  
Stimulation Of

Background Individuals with spinal cord injury may undergo multiple surgical procedures; however, it is not clear how spinal cord injury affects anesthetic requirements and movement force under anesthesia during both acute and chronic stages of the injury. Methods The authors determined the isoflurane minimum alveolar concentration (MAC) necessary to block movement in response to supramaximal noxious stimulation, as well as tail-flick and hind paw withdrawal latencies, before and up to 28 days after thoracic spinal transection. Tail-flick and hind paw withdrawal latencies were measured in the awake state to test for the presence of spinal shock or hyperreflexia. The authors measured limb forces elicited by noxious mechanical stimulation of a paw or the tail at 28 days after transection. Limb force experiments were also conducted in other animals that received a reversible spinal conduction block by cooling the spinal cord at the level of the eighth thoracic vertebra. Results A large decrease in MAC (to </= 40% of pretransection values) occurred after spinal transection, with partial recovery (to approximately 60% of control) at 14-28 days after transection. Awake tail-flick and hind paw withdrawal latencies were facilitated or unchanged, whereas reflex latencies under isoflurane were depressed or absent. However, at 80-90% of MAC, noxious stimulation of the hind paw elicited ipsilateral limb withdrawals in all animals. Hind limb forces were reduced (by >/= 90%) in both chronic and acute cold-block spinal animals. Conclusions The immobilizing potency of isoflurane increases substantially after spinal transection, despite the absence of a baseline motor depression, or "spinal shock." Therefore, isoflurane MAC is determined by a spinal depressant action, possibly counteracted by a supraspinal facilitatory action. The partial recovery in MAC at later time points suggests that neuronal plasticity after spinal cord injury influences anesthetic requirements.

Actions of norepinephrine on rat hypoglossal motoneurons

1995 ◽  
Vol 74 (5) ◽  
pp. 1911-1919 ◽  
Author(s):  
M. A. Parkis ◽  
D. A. Bayliss ◽  
A. J. Berger
Keyword(s):  
Choline Chloride ◽  
Reversal Potential ◽  
Repetitive Firing ◽  
Inward Current ◽  
Hypoglossal Motoneurons ◽  
Beta Adrenoceptor ◽  
Adrenoceptor Antagonist ◽  
Perfusion Solution ◽  
Adrenoceptor Agonist ◽  
Firing Properties

1. We used conventional intracellular recording techniques in 400-microns-thick slices from the brain stems of juvenile rats to investigate the action of norepinephrine (NE) on subthreshold and firing properties of hypoglossal motoneurons (HMs). 2. In recordings in current-clamp mode, 50 or 100 microM NE elicited a reversible depolarization accompanied by an increase in input resistance (RN) in all HMs tested (n = 74). In recordings in single-electrode voltage-clamp mode, NE induced a reversible inward current (INE) accompanied by a reduction in input conductance. The average reversal potential for INE was -104 mV. The NE responses could be elicited in a Ca(2+)-free solution containing tetrodotoxin, indicating that they were postsynaptic. 3. The NE response could be blocked by the alpha-adrenoceptor antagonist prazosin, but not by the beta-adrenoceptor antagonist propranolol, and could be mimicked by the alpha 1-adrenoceptor agonist phenylephrine but not by the alpha 2-adrenoceptor agonist UK 14,304 or by the beta-adrenoceptor agonist isoproterenol when alpha-adrenoceptors were blocked. 4. Substitution of barium for calcium in the perfusion solution blocked the increase in RN in response to NE without completely blocking the depolarization. Replacement of sodium chloride with choline chloride in the barium-substituted perfusion solution blocked the remaining depolarization. 5. The neuropeptide thyrotropin-releasing hormone (TRH), which also depolarizes and increases the RN of HMs, occluded the response of HMs to NE. 6. NE altered HM firing properties in three ways: it always lowered the minimum amount of injected current needed to elicit repetitive firing, it increased the slope of the firing frequency versus injected current relation in 8 of 14 cells tested, and it increased the delay from the onset of the depolarizing current pulse to the first evoked spike in all cells tested. 7. We conclude that NE acts directly on alpha 1-adrenoceptors to increase the excitability of HMs. It does this by reducing a barium-sensitive resting potassium current and activating a barium-insensitive inward current carried primarily by sodium ions. A portion of the intracellular pathway for these actions is shared by TRH. In addition, there is evidence that NE alters HM firing patterns by affecting currents that are activated following depolarization.

scholarly journals Hydrogen Diffusion Coefficient, Hydrogen Solution Coefficient and Hydrogen Permeability of Nb-TiNi Eutectic Alloy

2010 ◽  
Vol 638-642 ◽  
pp. 1131-1136
Author(s):  
Wei Liang Wang ◽  
Kazuhiro Ishikawa ◽  
Kiyoshi Aoki
Keyword(s):  
Diffusion Coefficient ◽  
Hydrogen Absorption ◽  
Hydrogen Diffusion ◽  
Hydrogen Permeability ◽  
K Value ◽  
Hydrogen Flow ◽  
Hydrogen Diffusion Coefficient ◽  
High K ◽  
Pressure Region ◽  
The Difference

In general, hydrogen permeabilityΦ of the alloy membrane is expressed as the product of the hydrogen diffusion coefficient D and the hydrogen solution coefficient K. Therefore, to improve the hydrogen permeability efficiently, the values of K and D should be separately considered. In the present study, hydrogen absorption and permeation behaviors of the Nb19Ti40Ni41 alloy consisting of the eutectic phase are investigated by measuring pressure-composition-isotherm (PCI) and by the hydrogen flow method and compared with those of palladium. The hydrogen absorption in the Nb19Ti40Ni41 alloy does not obey the Sieverts’ law in the pressure region of 0-1.0MPa at 523K, but it shows linear relationship between the difference in the square root of hydrogen pressure and hydrogen content between 0.1 and 0.4MPa. Although the value of D for the Nb19Ti40Ni41 alloy is considerably lower than that of palladium, its high K value enhances the hydrogen permeability Φ. It is suggested that the enhancement of D by microstructural control for Nb19Ti40Ni41 alloy is effective for improvement of Φ.

scholarly journals Differential in vivo Sensitivity of Melanophores and Xanthophores to Catecholamines in Winter Flounder (Pseudopleuronectes Americanus Walbaum) Integumentary Patterns

1985 ◽  
Vol 114 (1) ◽  
pp. 649-659
Author(s):  
D. Burton
Keyword(s):  
Winter Flounder ◽  
Pseudopleuronectes Americanus ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Albedo Change ◽  
Differential Responses

The catecholamines, adrenalin, dopamine and noradrenalin induce differential aggregation of melanophores in black-adapted winter flounder, Pseudopleuronectes americanus, paralleling patterning responses to albedo change. These differential responses to catecholamines suggest that the patterning mechanism in this species is largely dependent on a balance between neural aggregating and dispersing elements. The α-adrenoceptor agonist phenylephrine evokes paling in all pattern components in blackadapted flounder, whilst the α-adrenoceptor antagonist phentolamine darkens white-adapted flounders. The α-adrenoceptor agonist isoproterenol and the α-adrenoceptor antagonist propranalol have no effect on chromatophores of white-adapted flounder, but induce pallor in blackadapted flounder, which is interpreted as non specific. Noradrenalin elicits patterning responses in chromatically decentralized flounder, although the duration of pallor is shorter. The xanthophores, which are dispersed by a pituitary factor, will aggregate in response to high catecholamine doses.

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