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T O Neild

Publications and source records attributed to T O Neild.

At least 19 recordsLinked to original sources
PubMed1992

Effects of neuropeptide Y and agonists selective for neuropeptide Y receptor sub-types on arterioles of the guinea-pig small intestine and the rat brain.

1. The actions of neuropeptide Y (NPY) and agonists selective for NPY receptor subtypes were examined on arterioles from the guinea-pig small intestine and the rat pia in order to characterize the receptors mediating the vasoconstrictor and potentiating effects of NPY. 2. A method was developed for measuring the potentiating effects of NPY in situations where it was not possible to obtain a full concentration-response relationship for the vasoconstrictor. NPY, 50 nM, had a greater potentiating effect on the guinea-pig intestinal arterioles than those from the rat pia. 3. NPY and the Y1-selective agonist, NPY[Leu31,Pro34], potentiated the constrictor responses to U46619 in both arterioles and responses to noradrenaline in the guinea-pig arterioles. There was marked desensitization of the potentiating effect, and cross-desensitization between NPY and NPY[Leu31,Pro34]. Both NPY and NPY[Leu31,Pro34] caused constriction of the rat pial arterioles but not of those from the guinea-pig intestine. 4. The Y2-selective agonist PYY(13-36) caused no potentiation or vasoconstriction and did not affect the potentiation by NPY or NPY[Leu31,Pro34]. 5. The potentiating and vasoconstrictor effects of NPY on these arterioles were mediated by Y1 receptors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1990

Hyperpolarization and relaxation of arterial smooth muscle caused by nitric oxide derived from the endothelium.

Stimulation of the endothelial lining of arteries with acetylcholine results in the release of a diffusible substance that relaxes and hyperpolarizes the underlying smooth muscle. Nitric oxide (NO) has been a candidate for this substance, termed endothelium-derived relaxing factor. But there are several observations that argue against the involvement of NO in acetylcholine-induced hyperpolarization. First, exogenous NO has no effect on the membrane potential of canine mesenteric arteries. Second, although haemoglobin (believed to bind and inactivate NO (refs 11-15)) and methylene blue (which prevents the stimulation of guanylate cyclase) inhibit relaxation, neither has an effect on hyperpolarization. Finally, nitroprusside, thought to generate NO in vascular smooth muscle, relaxes rat aorta without increasing rubidium efflux. Nevertheless, nitrovasodilators, nitroprusside and nitroglycerin cause hyperpolarization in some arteries. NO might therefore be responsible for at least part of the hyperpolarization induced by acetylcholine. We now report that hyperpolarization and relaxation evoked by acetylcholine are reduced by NG-monomethyl-L-arginine, an inhibitor of NO biosynthesis from L-arginine. Thus NO derived from the endothelium can cause hyperpolarization of vascular smooth muscle, which might also contribute to relaxation by closing voltage-dependent calcium channels. Our findings raise the possibility that hyperpolarization might be a component of NO signal transduction in neurons or inflammatory cells.

Acetylcholine↗
PubMed1990

Actions of neuropeptide Y on arterioles of the guinea-pig small intestine are not mediated by smooth muscle depolarization.

Neuropeptide Y was applied to arterioles of the submucosa of the guinea-pig small intestine while arteriole diameter and smooth muscle membrane potential were monitored. Neuropeptide Y (50 nM-1 microM) caused no smooth muscle depolarization, and caused a small constriction in only 15 out of 38 arterioles studied. 50 nM Neuropeptide Y increased the amplitude of constriction caused by noradrenaline or brief trains of nerve stimulation, showing that it potentiated the effects of vasoconstrictors as it does in other arteries. The factor by which the amplitude was increased was greatest for small constrictions. Neuropeptide Y reduced the amplitude of the excitatory junction potential, suggesting that it decreased neurotransmitter release. These results show that the potentiating action of Neuropeptide Y does not depend on smooth muscle depolarization.

Animals↗
PubMed1990

Response of the rat tail artery to prolonged exposure to noradrenaline.

1. The contractions of the rat tail artery in response to noradrenaline applied for 30 min periods were recorded under conditions that potentiate the vascular escape phenomenon (spontaneous partial relaxation in the continued presence of a vasoconstrictor) in smaller arteries. 2. The conditions were elevated temperature (from 32-37 degrees C), 500 nM forskolin and 10 microM 3-isobutyl-1-methyl xanthine. 3. None of these conditions caused any change in the time-course of constriction in response to noradrenaline, or produced any evidence of vascular escape in this large artery.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Vasodilatation of arterioles by acetylcholine released from single neurones in the guinea-pig submucosal plexus.

The nervous control of arterioles in the guinea-pig submucosal plexus was studied. Outside diameters of arterioles were recorded using a video-monitoring system. Changes in arteriolar diameter in response to electrical stimulation of single neurones or ganglia in the plexus were measured. 2. When the arteriole was pre-constricted with the prostaglandin analogue U46619 or with phenylephrine, electrical stimulation (2-20 Hz, 10 s) of a ganglion dilated the blood vessel. This vasodilatation was abolished by tetrodotoxin or by cutting the fine nerve strands running between the ganglion and the arteriole. 3. The vasodilatations caused by ganglionic stimulation were blocked by the muscarinic antagonists atropine, pirenzepine, (11[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepine-6-)-one (AFDX-116), 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) and hexahydrosilodifenidol (HSDF). IC50 values for the inhibition of nerve-evoked vasodilatation by pirenzepine, AFDX-116 and HSDF were 500 nM, 4 microM and 25 nM respectively. Physostigmine (1 microM) increased the dilatation by 90%. 4. Muscarine dilated all submucosal arterioles; the concentration causing half-maximum effects was 200 nM. Muscarinic vasodilatations were inhibited by pirenzepine, AFDX-116, and HSDF in a competitive manner; dissociation equilibrium constants determined by Schild analyses were 125 nM, 1.3 microM and 4 nM respectively. 5. Gossypol, an irreversible inhibitor of the production of endothelium-derived relaxing factor (EDRF), did not reduce the vasodilatation produced by either ganglionic stimulation or muscarine in submucosal arterioles. 6. Intracellular recordings were made from submucosal neurones and action potentials were elicited by depolarizing current pulses (10 ms duration, 10 Hz/10 s). In seven neurones vasodilatation was associated with intracellularly evoked action potentials; this vasodilatation was blocked by pirenzepine. Cell bodies of reidentified vasodilator neurones were subsequently shown to contain immunoreactive choline acetyltransferase. 7. These results show that cholinergic neurones in the submucosal plexus project to submucosal arterioles and that they release acetylcholine onto muscarinic receptors to produce vasodilatation. The muscarinic receptor activated by nerve-released acetylcholine is the M3 subtype and its location appears to be on the vascular smooth muscle rather than the endothelium.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1989

A study of the phasic response of arterioles of the guinea pig small intestine to prolonged exposure to norepinephrine.

Arterioles of the guinea pig small intestine constricted in response to norepinephrine, but the constriction was not maintained. The duration of constriction was reduced after pretreatment by theophylline, 3-isobutyl-1-methyl-xanthine, bromo-cAMP, or bromo-cGMP, suggesting that the relaxation was related to an increase in cyclic nucleotide levels in the cell. Forskolin also reduced the duration of constriction, suggesting the involvement of cAMP. The duration of constriction was not affected by propranolol or isoprenaline, indicating no involvement of beta adrenoceptors. A scheme to explain these observations, in which alpha 1-adrenoceptor activation stimulates adenylate cyclase, leading to a rise in cAMP and an increased rate of intracellular calcium sequestration is proposed. The resulting fall in intracellular calcium leads to repolarization and relaxation.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Relaxation and hyperpolarization of the smooth muscle of the rat tail artery following electrical stimulation.

1. The smooth muscle of the rat tail artery was made to constrict with noradrenaline or 5-hydroxytryptamine. Electrical stimulation of the contracted artery caused a transient hyperpolarization and relaxation. 2. The hyperpolarization and relaxation could be recorded from denervated arteries, showing that these responses were independent of the perivascular nerves. 3. Removal of the vascular endothelium caused only a small reduction in the relaxation. 4. Raising the external K+ concentration to 20 mM abolished or greatly reduced the relaxation, and caused some reduction of the hyperpolarization. 5. 1 mM-tetraethylammonium chloride abolished both the hyperpolarization and the relaxation. 6. From the membrane potential-contraction relationship for this artery it appeared that the hyperpolarization could account for some but not all of the relaxation.

Animals↗
PubMed1988

Electrophysiological properties of the mesenteric artery of the rabbit with perinephritis hypertension.

Membrane potential and tension were simultaneously recorded in ileal arteries isolated from rabbits with perinephritis hypertension and from sham operated controls. Stimulation of perivascular nerves with single pulses produced excitatory junction potentials, action potentials and contraction. Setting resting tension to levels equivalent to intraluminal pressures of 23, 70 and 114 mm Hg had no effect on the resting membrane potential, excitatory junction potential amplitude, action potential threshold or membrane time constant. The resting membrane potential in arteries from hypertensive rabbits was 3.7 mV less negative than in the shams. There were no significant changes in the action potential threshold or membrane time constant. It is suggested that the changes observed in the membrane potential may contribute to the increased responsiveness found in arteries from this model of hypertension.

Animals↗
PubMed1987

Membrane properties of rabbit basilar arteries and their responses to transmural stimulation.

Changes in membrane potential of rabbit basilar arteries were recorded in response to transmural stimuli applied by means of a suction electrode. Responses to current pulses of long duration and low intensity showed that the passive electrical properties of basilar arteries were similar to those of other vascular smooth muscles. In contrast to peripheral arteries, action potentials were readily evoked by depolarizing currents. Action potentials were graded in amplitude from 17-60 mV according to stimulus strength. Amplitudes and rates of rise of the directly evoked action potentials increased with increasing external calcium and were abolished by cobalt, manganese and magnesium. Brief electrical stimuli which might have been expected to activate perivascular nerves produced slow depolarizing responses whose amplitude and duration increased with increasing stimulus intensity. These responses were not blocked by tetrodotoxin, lowered external calcium, or sympathetic denervation. They do not appear to be due to the release of a conventional neurotransmitter.

Animals↗
PubMed1987

Effects of denervation on the responses of the rat tail artery to alpha beta-methylene ATP.

1. One microM alpha beta-methylene ATP (alpha beta meATP) caused transient contraction and depolarization of the smooth muscle of the rat tail artery. 2. The peak contraction was greater in denervated arteries; the peak depolarization was the same in normal and denervated arteries. 3. This suggests that alpha beta meATP receptors do not increase following denervation. 4. In denervated arteries electrical stimulation produced depolarizing responses that were not due to neurotransmitter release but which were blocked by alpha beta meATP. 5. It is suggested that alpha beta meATP may be a blocker of cation channels.

Adenosine Triphosphate↗
PubMed1987

Actions of neuropeptide Y on innervated and denervated rat tail arteries.

1. Neuropeptide Y caused a dose-dependent contraction and depolarization of the smooth muscle of the rat tail artery. 2. 30 nM-neuropeptide Y increased the contraction caused by either nerve-released noradrenaline or smooth muscle action potentials. 3. 30 nM-neuropeptide Y did not change the amplitude or rate of rise of the smooth muscle action potential. It did not change the amplitude of small excitatory junction potentials, suggesting that it did not affect neurotransmitter release. 4. 30 nM-neuropeptide Y increased the contraction caused by exogenous noradrenaline, 5-hydroxytryptamine and K in concentrations that gave submaximal contractions. It did not affect the response to higher concentrations that gave maximal or near-maximal contractions.

Action Potentials↗
PubMed1987

Relation between membrane potential and contractile force in smooth muscle of the rat tail artery during stimulation by norepinephrine, 5-hydroxytryptamine, and potassium.

The relation between smooth muscle membrane potential and contractile force was investigated in the rat tail artery to assess the importance of smooth muscle depolarization in the control of smooth muscle tone. Smooth muscle membrane potential and contractile force were measured simultaneously in isolated pieces of rat tail artery exposed to a range of concentrations of norepinephrine, 5-hydroxy-tryptamine, or raised external potassium. Potassium caused depolarization and contraction when the membrane was depolarized beyond -40 mV. Maximum contraction occurred at -19 mV, and further depolarization gave no increase in contraction. Both norepinephrine and 5-hydroxytryptamine caused contraction and depolarization, but the relation between depolarization and contraction was not the same as when potassium was used. There was significant contraction when the membrane potential was more negative than -50 mV, and the membrane potential was around -30 mV during maximal contractions. Although they acted on pharmacologically different membrane receptors, the relation between membrane potential and contraction was the same for norepinephrine and 5-hydroxytryptamine. Prazosin reduced the responses to norepinephrine but did not change the relation between membrane potential and contractile force. These results indicated that norepinephrine and 5-hydroxytryptamine binding to their respective receptors might activate the same sets of intracellular processes that subsequently caused both depolarization and contraction.

Animals↗
PubMed1986

Effects of alpha beta methylene ATP on membrane potential, neuromuscular transmission and smooth muscle contraction in the rat tail artery.

alpha beta methylene ATP (meATP, 400 nM-1 microM) caused depolarization and constriction of the smooth muscle of the rat tail artery, and block of the excitatory junction potential (e.j.p.). A similar depolarization caused by 25 mM K did not block the e.j.p. Contractions caused by nerve-released noradrenaline acting on alpha-adrenoceptors were potentiated by meATP but this was probably due to the depolarization as 25 mM K had a similar effect. MeATP blocked e.j.p.s recorded in the presence of 3 microM tetrodotoxin, suggesting that meATP was not blocking e.j.p.s by a local anaesthetic action.

Adenosine Triphosphate↗
PubMed1986

Effects of endothelium-derived relaxing factor on the smooth muscle of the rat tail artery.

Simultaneous measurements of smooth muscle membrane potential and tension were made from isolated pieces of rat tail artery. A single electrical stimulus to the perivascular nerves produced a transient contraction of the smooth muscle. The amplitude of the contraction was increased after removal of the endothelium. The excitatory junction potentials and action potentials in the smooth muscle had the same amplitudes before and after removal of the endothelium. Tension obtained by direct stimulation of the arterial muscle in guanethidine-treated arteries was also increased by removal of the endothelium. When the artery was constricted by noradrenaline or 5-hydroxytryptamine, electrical stimulation caused a relaxation that was reduced by removing the endothelium. It was concluded that the electrical stimulus released the endothelium-derived relaxing factor (EDRF) which reduced the amount of contractile force that could be produced by an action potential in the smooth muscle.

Action Potentials↗
PubMed1986

An in vitro study of the pharmacological and electrophysiological properties and the adrenergic innervation of small pulmonary arteries from children with pulmonary hypertension.

A study was made of the pharmacological and electrophysiological properties of pieces of small intrapulmonary arteries (100-450 micron I.D.) taken from children with cardiac defects that caused the pulmonary circulation to be exposed to an abnormally high perfusion pressure. The sensitivity of the arterial smooth muscle to the constrictor agonists acetylcholine and 5-hydroxytryptamine was similar to that reported for adult pulmonary arteries. Norepinephrine or histamine caused little or no constriction, although both these substances have been reported to be powerful constrictors of adult pulmonary arteries. The electrophysiological properties were similar to those of the smooth muscle of systemic arteries. The mean resting membrane potential was -6.12 mV +/- 1.29 (SEM n = 16). Stimulation of the perivascular nerves produced excitatory junction potentials, but no smooth muscle action potentials were recorded. Histochemical investigation revealed catecholamine containing nerve fibres around all intrapulmonary arteries down to 40 micron I.D.

Acetylcholine↗