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J L Morris

Publications and source records attributed to J L Morris.

At least 37 records · Page 2Linked to original sources
PubMed1998

Regional differences in sympathetic neurotransmission to cutaneous arteries in the guinea-pig isolated ear.

The effects of sympathetic nerve stimulation on different cutaneous arteries were examined in arteries isolated from guinea-pig ears, by measuring membrane potential changes in smooth muscle cells in response to electrical field stimulation. Resting membrane potential (RMP) was similar in proximal (main ear artery) and distal (3rd or 4th branch order) cutaneous arteries (mean -71 mV). Single stimuli evoked excitatory junction potentials (EJPs) in all arteries. The EJPs in proximal arteries were twice the amplitude, and the time constant of EJP decay was almost half the value, compared with distal cutaneous arteries. EJP amplitude was reduced by > 90% by suramin (30 microM) or alpha,beta,methylene-ATP (alpha,beta,m-ATP)(1 microM) in all proximal, and most distal arteries. Residual responses in distal arteries were resistant to tetrodotoxin. The N-type calcium channel blocker, omega-conotoxin GVIA (30 nM), reduced EJP amplitude by 70-100% in both proximal and distal arteries. Successive EJPs evoked by trains of stimuli at 1 to 5 Hz were depressed in amplitude in proximal arteries, but showed facilitation in distal arteries. EJP depression in proximal arteries was reversed to facilitation by the alpha2-adrenoceptor antagonist, yohimbine (30 nM). Trains of stimuli delivered at 10-20 Hz produced summation of EJPs and active membrane responses in 30% of proximal arteries. Active responses were never detected in distal arteries. Slow depolarizations following the EJPs were detected in most arteries after trains of stimuli, and were abolished by prazosin (0.3 microM) or omega-conotoxin GVIA (30 nM). The density of the perivascular plexus of axons innervating proximal arteries, demonstrated with catecholamine fluorescence histochemistry, was twice that in distal cutaneous arteries. These regional differences in sympathetic neurotransmission suggest that cutaneous vasoconstriction in response to thermoregulatory stimuli, which occurs predominantly in distal cutaneous segments, is likely to be qualitatively different from cutaneous vasoconstriction of proximal arteries in response to other physiological stimuli.

Adrenergic alpha-Antagonists↗
PubMed1998

Neurochemical distinction between skeletal muscle vasodilator neurons and pelvic vasodilator neurons in guinea-pigs.

This study sets out to compare the combinations of potential vasodilator transmitters expressed by sympathetic and pelvic vasodilator neurons of guinea-pigs. Triple-labelling fluorescence immunohistochemistry was used to examine immunoreactivity (IR) to vasoactive intestinal peptide (VIP), nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP) in lumbar sympathetic ganglia, and in perivascular axons supplying hindlimb skeletal muscles or pelvic viscera. Only 0.2% of VIP-IR nerve cell bodies in lumbar sympathetic ganglia (n = 4632 VIP-IR nerve cell profiles) contained NOS-IR, and one VIP-IR neuron contained CGRP-IR. The VIP-IR perivascular axons along the common and external iliac arteries, femoral artery and arteries to hindlimb muscles lacked NOS-IR and CGRP-IR. In contrast, all VIP-IR perivascular axons projecting from pelvic ganglia to the main uterine artery, and half of the VIP-IR axons along the internal iliac artery, contained NOS-IR and CGRP-IR. Thus, the neurochemical content of sympathetic vasodilator neurons to skeletal muscle arteries was clearly distinguishable from that of pelvic vasodilator neurons to the uterine vasculature. Furthermore, the autonomic dilation in each vascular bed is likely to be qualitatively different, and matched to the functional requirements of each target organ.

Animals↗
PubMed1998

Peripheral fields of sympathetic vasoconstrictor neurons in guinea pigs.

We have combined retrograde axonal tracing using Fast Blue and Dil, with immunohistochemistry, to estimate the maximum size of peripheral fields of identified sympathetic vasoconstrictor neurons projecting to guinea-pig ear tips. Many neurons in the superior cervical ganglia were labelled with both Fast Blue and Dil after dye injections up to 7 mm apart. Few neurons were labelled when dye injections were 8-10 mm apart. Neurons labelled with both Dil and Fast Blue after dye injections 5-7 mm apart had, on average, larger somata (436 +/- 84 microm2, mean +/- SEM, n = 47) than neurons labelled with Dil only (388 +/- 11 microm2, n = 147). Typically, 50-100 neurons innervated a region of vasculature 1 mm in diameter. We conclude that sympathetic vasoconstrictor neurons branch widely before converging on to their target blood vessels. Progressive recruitment of vasoconstrictor neurons with increasing field size would provide an efficient mechanism for graded neural control of the circulation.

Amidines↗
PubMed1998

Repair of coronary artery perforation after rotastenting by implantation of the JoStent covered stent.

Coronary artery perforation is an unusual but well recognised complication of Percutaneous Transluminal Coronary Angioplasty (PTCA) and coronary atherectomy and may lead to hemopericardium and cardiac tamponade. If the perforation cannot be sealed by prolonged inflation with a perfusion balloon catheter, emergency cardiac surgery is usually necessary. This case report describes the potential use of a "covered" coronary artery stent for sealing perforations in the coronary circulation.

Atherectomy, Coronary↗
PubMed1997

Five inhibitory transmitters coexist in pelvic autonomic vasodilator neurons.

Here we describe the localization of a potent vasodilator, calcitonin gene-related peptide (CGRP), in pelvic autonomic neurons containing four other inhibitory transmitters: vasoactive intestinal peptide (VIP), neuropeptide Y, nitric oxide and acetylcholine. These neurons mediate endothelium-independent vasodilation by releasing nitric oxide and one or more neuropeptides. Sixty percent of nerve cell bodies in guinea-pig paracervical ganglia with immunoreactivity (IR) for VIP, choline acetyltransferase (ChAT) and nitric oxide synthase (NOS), also contained IR for CGRP. Furthermore, many VIP-IR varicose nerve terminals at the adventitia-medial junction of the guinea-pig uterine artery contained IR for CGRP, ChAT and NOS. Both alpha-hCGRP and beta-hCGRP were potent dilators of the uterine artery (pD2 values 8.1, 8.3, respectively), but 1 microM hCGRP(8-37) did not antagonize dilations produced by either agonist. Dilations produced by alpha-hCGRP were unaffected by removal of the endothelium. Taken together with results of our previous studies, we propose that CGRP can contribute directly to autonomic vasodilation, possibly via CGRP2 receptors on smooth muscle cells, and that CGRP is the fifth inhibitory transmitter co-existing in pelvic vasodilator neurons.

Animals↗
PubMed1997

Selective innervation of different target tissues in guinea-pig cranial exocrine glands by sub-populations of parasympathetic and sympathetic neurons.

This study has used multiple-labelling immunohistochemistry and quantitative analysis to examine the projections of subpopulations of parasympathetic and sympathetic neurons to different vascular and secretory structures in five cranial exocrine glands of guinea-pigs. Multiple subpopulations of parasympathetic axons, identified by immunoreactivity (IR) for various combinations of peptides, innervated arteries, arterioles, ducts and acini in sublingual, submandibular, parotid, lacrimal and zygomatic glands, although axons were absent from ducts in the parotid gland. Most parasympathetic axons contained IR for vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), with or without enkephalin (Enk). The proportion of parasympathetic axons that contained Enk-IR varied greatly between target tissues and glands: Enk-IR was more common in axons supplying secretory ducts, acini and arterioles than in axons innervating more proximal arteries; Enk-IR was less common in axons supplying the lacrimal gland than axons supplying the submandibular, lacrimal and zygomatic glands. Sympathetic axons with IR for tyrosine hydroxylase (TH) innervated arterial vessels in all glands, but innervated secretory structures only in the salivary glands. Sympathetic axons supplying proximal arterial segments often contained NPY-IR and sometimes also contained IR for dynorphin. Dynorphin-IR was more common in axons in the parotid, lacrimal and zygomatic glands than in the sublingual and submandibular glands. In contrast, axons supplying arterioles, ducts and acini lacked peptide IR. These results indicate that neuronal pathways regulating proximal arteries in cranial exocrine glands are different from the neuronal pathways regulating arterioles and acini, and may be different from neurons projecting to proximal secretory ducts. Furthermore, the peptides enkephalin, NPY and dynorphin are likely to make variable contributions to autonomic neurotransmission in different arterial segments and in different cranial exocrine glands.

Animals↗
PubMed1996

Non-noradrenergic sympathetic neurons project to extramuscular feed arteries and proximal intramuscular arteries of skeletal muscles in guinea-pig hindlimbs.

This study set out to examine the non-noradrenergic sympathetic innervation of extramuscular and intramuscular arterial vessels supplying hindlimb muscles of guinea-pigs, using multiple-labelling fluorescence immunohistochemistry. Non-noradrenergic axons, identified by their immunoreactivity (IR) to vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), innervated nearly all (> or = 88%) extramuscular feed arteries supplying muscles of the medial thigh. The distribution of non-noradrenergic axons along extramuscular feed arteries was often patchy, with increased density near some branch points. The density of axons with VIP-IR and NPY-IR at the adventitia-medial junction of the largest extramuscular arteries was similar to the density of noradrenergic axons identified by IR to tyrosine hydroxylase (TH) and NPY. The proportion of arterial vessels innervated by VIP-IR axons decreased in more distal, intramuscular arterial segments, and when present, the VIP-IR axons were fewer in number than TH-IR axons innervating the same segments. Distal arterioles (< 20 microns diameter) were never innervated by VIP-IR axons, but always by TH-Ir axons. The non-noradrenergic sympathetic neurons are almost certainly vasodilator neurons. The prominent innervation of extramuscular feed arteries by sympathetic non-noradrenergic neurons has not been reported previously, even in cats and dogs where there is good physiological evidence for a sympathetic vasodilator response in skeletal muscles. The present morphological results provide compelling reasons for re-evaluating the functional role of sympathetic vasodilation in skeletal muscles of rodents, particularly in relation to the role of feed arteries in neural regulation of muscle blood flow.

Animals↗
PubMed1996

Sympathetic vasoconstrictor neurons projecting from the guinea-pig superior cervical ganglion to cutaneous or skeletal muscle vascular beds can be distinguished by soma size.

We have used a combination of retrograde axonal tracing and intracellular dye injections to determine the soma size of sympathetic vasoconstrictor neurons projecting from the superior cervical ganglion to the cutaneous vascular bed of the eartips, or to the vascular beds of the masseter muscle, of guinea-pigs. Neurons projecting to vasculature of the masseter muscle had a cross-sectional area of 956 +/- 295 microns2 (mean +/- SD; n = 45 cells) and were significantly larger than neurons projecting to the vasculature of the eartip skin (mean cross-sectional area +/- SD, 604 +/- 251 microns2; n = 39 cells). These results are consistent with physiological observations showing that muscle vasoconstrictor neurons have faster conduction velocities than cutaneous vasoconstrictor neurons. Furthermore, they suggest that muscle vasoconstrictor neurons may innervate a larger volume of vasculature compared with cutaneous vasoconstrictor neurons.

Animals↗
PubMed1996

Projections of intrinsic cardiac neurons to different targets in the guinea-pig heart.

We set out to determine the projections of the major immunohistochemically-defined populations of intrinsic cardiac neurons to different target tissues within the guinea-pig heart. Ultrastructural studies, and immunoreactivity to the neuronal marker, neuron-specific enolase, suggested that the number of axons of intrinsic neurons in most regions of the heart was low when compared with the populations of axons projecting from extrinsic sensory and sympathetic ganglia. Multiple-labelling immunofluorescence was used to demonstrate the terminals of the major populations of peptide-containing intrinsic neurons. The intrinsic nature of peptide-containing axons was confirmed by long-term organotypic culture of cardiac tissue, which resulted in degeneration of axons of extrinsic neurons. The relative density and peptide content of intrinsic axons throughout the heart was not consistent with the relative proportions of peptide-containing intracardiac nerve cell bodies observed previously. The most commonly-encountered axons contained immunoreactivity (IR) to vasoactive intestinal peptide (VIP) alone, although nerve cell bodies with VIP constituted less than 5% of the total population of intrinsic neurons. Populations of axons containing IR to somatostatin alone, somatostatin and substance P, neuropeptide Y (NPY) alone, somatostatin and NPY, or VIP and NPY, also were observed. Intrinsic axons containing substance P-IR were very rare, much more so than would be predicted from the peptide content of intrinsic nerve cell bodies. The regions of the heart with the most dense innervation by axons of intrinsic neurons were the cardiac valves, the atrio-ventricular node and the sino-atrial node. Each of these targets was innervated by several populations of peptide-containing axons. Thus, each population of peptide-containing intrinsic neurons projected to a variety of target tissues within the heart. One possible interpretation of these results is that immunohistochemically-distinct populations of intrinsic neurons belong to different functional classes of neurons (sensory neurons, interneurons, final motor neurons), each of which innervates many regions of the heart.

Animals↗
PubMed1996

Multicenter, placebo-controlled trial of cabergoline taken once daily in the treatment of Parkinson's disease.

Cabergoline is a dopaminergic agonist relatively specific for the D2 receptor and much longer-acting than other dopamine agonists. We conducted a randomized, placebo-controlled, double-blind study of cabergoline in 188 levodopa/carbidopa-treated patients with suboptimally controlled Parkinson's disease (PD). The cabergoline patients had significantly better Activities of Daily Living (p = 0.032) and Motor Examination (p = 0.031) scores at the conclusion of the trial compared with the placebo group. The daily levodopa dose for the cabergoline patients decreased 18% compared with a 3% reduction for the placebo group (p < 0.001). The amount of time in the "on" state increased more in the cabergoline group (p = 0.022). The side-effect was similar to that seen with other dopamine agonists, and cabergoline was generally well tolerated. We conclude that cabergoline is an effective adjunct to levodopa for the treatment of PD.

Activities of Daily Living↗
PubMed1995

ISIS-4.

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Humans↗
PubMed1995

Peptides as neurotransmitters in vascular autonomic neurons.

1. Neuropeptides are present in the majority of autonomic neurons projecting to blood vessels, where they are co-localized with non-peptide transmitters and sometimes with other peptides. 2. Neuropeptides are released from vasoconstrictor and vasodilator nerve terminals after high frequency stimulation ( > 2-5Hz) with trains of impulses. 3. Neuropeptides can have potent post-synaptic effects on vascular tone, but often these effects are restricted to selected regions of the vasculature. 4. Post-synaptic effects of neuropeptides tend to be more slowly-developing and more long-lasting than those of non-peptide transmitters. 5. Autonomic vasoconstrictor and vasodilator responses often have multiple phases, with the faster phases being mediated by non-peptide transmitters and the slower phases medicated predominantly by one or more neuropeptides. 6. Some neuropeptides do not seem to have post-synaptic effects in a particular vascular bed, but can have presynaptic actions on neurotransmitter release. 7. Neuropeptides form an important component of the repertoire of neurotransmitters used by vascular autonomic neurons to regulate regional blood flow in response to a range of physiological stimuli.

Animals↗
PubMed1995

Nitrates in myocardial infarction: influence on infarct size, reperfusion, and ventricular remodelling.

OBJECTIVE: To assess the possible benefits of intravenous isosorbide dinitrate in acute myocardial infarction and oral isosorbide mononitrate in subacute myocardial infarction. METHODS: 316 patients presenting with acute myocardial infarction were entered into double blind placebo controlled clinical trials assessing infarct size by enzyme release, ventricular size and function by echocardiography, reperfusion by continuous 12 lead ST segment monitoring and late potentials by high resolution electrocardiography. RESULTS: 301 patients, of whom 292 (97%) received thrombolytic treatment, were randomised on admission to intravenous isosorbide dinitrate or placebo. Overall, there was no significant effect of treatment on infarct size, ST segment resolution, ventricular remodelling, or late potentials at day 3. A trend was observed towards a reduction in infarct size in patients with non-Q wave infarction treated with isosorbide dinitrate. Heterogeneity of nitrate effect was observed in relation to the degree of ST segment elevation on presentation with a clear benefit of isosorbide dinitrate in patients with moderate ST segment elevation (472 U/l v 704 U/l, P = 0.003) and a trend towards a deleterious effect in patients with marked ST segment elevation (1152 U/l v 1058 U/l, P = 0.2). ST segment re-elevation was more common among patients receiving nitrate treatment than in those assigned to placebo (29 v 16, P < 0.05). Some 160 patients underwent a further randomisation to sustained release isosorbide mononitrate or placebo on day 3. Echocardiographic volumes after 6 weeks of treatment were similar in the two groups. CONCLUSIONS: No benefit was observed with administration of nitrates in the treatment groups as a whole for either acute or subacute infarction. There was, however, evidence of heterogeneity of effect in the different subgroups of acute infarction, and the possibility that nitrates may have differing actions in different groups of patients should be considered.

Aged↗
PubMed1995

Roles of peptides and other substances in cotransmission from vascular autonomic and sensory neurons.

Blood vessels may be innervated by up to three major classes of neurons: sympathetic vasoconstrictor neurons; sympathetic or parasympathetic vasodilator neurons; and peripheral fibres of small diameter sensory neurons, which can mediate vasodilation. Most vascular neurons utilise multiple transmitters, including neuropeptides and small nonpeptides such as ATP or nitric oxide, often in addition to noradrenaline or acetylcholine. Subpopulations of each major class of vascular neurons innervating different vascular segments may contain different combinations of neurotransmitters. Furthermore, the same population of neurons can release different cotransmitters in response to different patterns of stimulation. In general, peptides mediate slower and more long lasting changes in vascular resistance than do nonpeptides. Thus, autonomic and sensory neurons are well adapted to produce qualitatively different vascular effects in response to different types of afferent input. The major challenge for the future is to develop new antagonists for many of the substances colocalised in vascular neurons, particularly neuropeptides. These agents will allow us to precisely determine the relative roles of multiple cotransmitters, and are likely to provide therapeutic agents that can be targeted to specific regions of the vasculature.

Animals↗