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Innervation and Functional Aspects of Neuropeptides in the Coronary Circulation.

Saetrum Opgaard, Ole (1996)
Abstract
A network of perivascular nerve fibres was demonstrated in coronary arteries and veins from guinea-pig and man. Nerve fibres displaying immunoreactivity to neuropeptide Y (NPY) had a distribution pattern similar to those containing immunoreactivity to tyrosine hydroxylase. Immunoreactivity to substance P and calcitonin gene-related peptide (CGRP) occurred in the same varicose nerve fibres, which were distinct from those displaying immunoreactivity to NPY, and NPY-immunoreactive nerve fibres were distinct from those displaying acetylcholinesterase activity. Only few nerve fibres positive for vasoactive intestinal peptide (VIP) were detected. Immunoreactivity to endothelin was demonstrated over the endothelium, and mRNA encoding the... (More)
A network of perivascular nerve fibres was demonstrated in coronary arteries and veins from guinea-pig and man. Nerve fibres displaying immunoreactivity to neuropeptide Y (NPY) had a distribution pattern similar to those containing immunoreactivity to tyrosine hydroxylase. Immunoreactivity to substance P and calcitonin gene-related peptide (CGRP) occurred in the same varicose nerve fibres, which were distinct from those displaying immunoreactivity to NPY, and NPY-immunoreactive nerve fibres were distinct from those displaying acetylcholinesterase activity. Only few nerve fibres positive for vasoactive intestinal peptide (VIP) were detected. Immunoreactivity to endothelin was demonstrated over the endothelium, and mRNA encoding the endothelin-A (ET-A) and the endothelin-B (ET-B) receptor were detected in human epicardial coronary arteries with and without endothelium and in human coronary veins. Vasomotor responses to different vasoactive substances were tested on isolated coronary vessels. Noradrenaline (NA) and adenosine 5'-triphosphate (ATP) induced mainly contraction of human epicardial coronary veins, whereas relaxant responses were more pronounced in human epicardial coronary arteries. Coronary arteries from older individuals were however more susceptible to NA-mediated contraction than those from younger persons. Relaxation of human epicardial coronary arteries induced by NA, isoprenaline and ATP were endothelium-independent. NPY had no direct vasomotor effect on human epicardial coronary arteries and veins, but in guinea-pig epicardial coronary arteries NPY inhibited relaxant responses induced by acetylcholine (ACh), VIP, substance P and isoprenaline. ACh induced strong contraction of human epicardial coronary arteries and veins, and at lower concentrations ACh induced endothelium-dependent relaxation of human epicardial coronary arteries. Substance P, CGRP and VIP potently relaxed coronary arteries and veins. In human epicardial coronary arteries, the relaxation to substance P was endothelium-dependent whereas the relaxation to CGRP seemed to be partially endothelium-dependent, and relaxation to VIP independent of an intact endothelium. Studies with different agonists and antagonists to ET-A and ET-B receptors suggested that contractions are mediated by the ET-A receptor and relaxations mediated by the ET-B receptor. The ET-B receptor mediated relaxation of human epicardial coronary arteries was endothelium-dependent. (Less)
Abstract (Swedish)
Popular Abstract in Swedish

Nätverk av nervtrådar påvisades kring koronara artärer och vener från marsvin och människa. Medelst immunhistokemiska metoder demonstrerades olika signalsubstanser i anknytning till dessa nervtrådar och i olika delar av kärlväggen (endotelet, media, adventitia), och det påvisades hur vissa av dessa substanser var lokaliserade i samma vesikler av ovan nämnda nervtrådar. Noradrenalin (NA), neuropeptid Y (NPY), substans P, kalcitonin gen-relaterad peptid (CGRP), acetylkolin (ACh) och vasoaktivt intestinalt polypeptid (VIP) påvisades i det yttre lagret av koronara artärer och vener (adventitia och gränsen mellan adventitia och media), där dessa substanser förmodas frisättas från nervtrådar.... (More)
Popular Abstract in Swedish

Nätverk av nervtrådar påvisades kring koronara artärer och vener från marsvin och människa. Medelst immunhistokemiska metoder demonstrerades olika signalsubstanser i anknytning till dessa nervtrådar och i olika delar av kärlväggen (endotelet, media, adventitia), och det påvisades hur vissa av dessa substanser var lokaliserade i samma vesikler av ovan nämnda nervtrådar. Noradrenalin (NA), neuropeptid Y (NPY), substans P, kalcitonin gen-relaterad peptid (CGRP), acetylkolin (ACh) och vasoaktivt intestinalt polypeptid (VIP) påvisades i det yttre lagret av koronara artärer och vener (adventitia och gränsen mellan adventitia och media), där dessa substanser förmodas frisättas från nervtrådar. Endothelin (ET) kunde däremot påvisas endast i det inre lagret (endotelet) av koronara artärer och vener, där denna mycket potenta kärlkontraherande substansen förmodas bildas i endotelceller. Vidare påvisades mRNA (som förenklat kan sägas vara budbäraren från en cells aktiva arvsmassa) för olika ET-receptorer i kärlväggen av humana koronara artärer och vener. Ovan nämnda substansers förmåga att påverka kärltonus samt effekten av olika antagonister (substanser som blockerar specifika receptorer) testades på isolerade, cirkulära ringsegment av koronara artärer och vener från marsvin och människa. En jämförelse av effekten av olika substanser på koronarartärer med och utan endotel gjordes också. Substans P, CGRP och VIP relaxerade både artärer och vener medan ET inducerade kraftig kontraktion. NPY hade ingen påvisbar effekt på kärltonus i humana koronara artärer eller vener. Däremot hämmade NPY den relaxerande effekten av ACh, substans P och VIP i koronarartärer från marsvin. ACh i relativt låga koncentrationer relaxerade humana koronarartärer medan högre koncentrationer gav kontraktion. För NA och adenosin trifosfat (ATP), som båda frisätts från sympatiska nerver, noterades påtagliga skillnader i effekt mellan humana koronara artärer och vener i form av kraftig kontraktion på vensidan och övervägande relaxation på artärsidan. NA hade dock en kraftigare kontraherande effekt på humana koronarartärer från äldre jämfört med yngre individer. Att olika signalsubstanser produceras eller frisätts i anknytning till koronarkärl, samt att de på ett uttalat sätt kan påverka kärltonus, indikerar en viktig roll i regleringen av koronarblodflödet och öppnar nya intressanta perspektiv beträffande förebyggande och behandling av koronar hjärtsjukdom. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Saxena, Pramod R., Erasmus University, Rotterdam, Holland
publishing date
type
Thesis
publication status
published
subject
keywords
immunohistochemistry., mRNA, receptors, ET-B, ET-A, endothelin, substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, acetylcholine, NPY, ATP, noradrenaline, nerves, sensory, parasympathetic, sympathetic, veins, Coronary, arteries, Endocrinology, secreting systems, diabetology, Endokrinologi, sekretion, diabetologi, Cardiovascular system, Kardiovaskulära systemet
pages
176 pages
publisher
Department of Internal Medcine, University Hospital of Lund,
defense location
University Hospital, Lund, Sweden
defense date
1996-04-26 10:15:00
external identifiers
  • other:ISRN: LUMEDW/MEMA--96(1047)--SE
language
English
LU publication?
no
id
c198097c-94e6-4fc1-9315-d86d9370a366 (old id 28478)
date added to LUP
2016-04-04 10:08:10
date last changed
2018-11-21 20:56:59
@phdthesis{c198097c-94e6-4fc1-9315-d86d9370a366,
  abstract     = {{A network of perivascular nerve fibres was demonstrated in coronary arteries and veins from guinea-pig and man. Nerve fibres displaying immunoreactivity to neuropeptide Y (NPY) had a distribution pattern similar to those containing immunoreactivity to tyrosine hydroxylase. Immunoreactivity to substance P and calcitonin gene-related peptide (CGRP) occurred in the same varicose nerve fibres, which were distinct from those displaying immunoreactivity to NPY, and NPY-immunoreactive nerve fibres were distinct from those displaying acetylcholinesterase activity. Only few nerve fibres positive for vasoactive intestinal peptide (VIP) were detected. Immunoreactivity to endothelin was demonstrated over the endothelium, and mRNA encoding the endothelin-A (ET-A) and the endothelin-B (ET-B) receptor were detected in human epicardial coronary arteries with and without endothelium and in human coronary veins. Vasomotor responses to different vasoactive substances were tested on isolated coronary vessels. Noradrenaline (NA) and adenosine 5'-triphosphate (ATP) induced mainly contraction of human epicardial coronary veins, whereas relaxant responses were more pronounced in human epicardial coronary arteries. Coronary arteries from older individuals were however more susceptible to NA-mediated contraction than those from younger persons. Relaxation of human epicardial coronary arteries induced by NA, isoprenaline and ATP were endothelium-independent. NPY had no direct vasomotor effect on human epicardial coronary arteries and veins, but in guinea-pig epicardial coronary arteries NPY inhibited relaxant responses induced by acetylcholine (ACh), VIP, substance P and isoprenaline. ACh induced strong contraction of human epicardial coronary arteries and veins, and at lower concentrations ACh induced endothelium-dependent relaxation of human epicardial coronary arteries. Substance P, CGRP and VIP potently relaxed coronary arteries and veins. In human epicardial coronary arteries, the relaxation to substance P was endothelium-dependent whereas the relaxation to CGRP seemed to be partially endothelium-dependent, and relaxation to VIP independent of an intact endothelium. Studies with different agonists and antagonists to ET-A and ET-B receptors suggested that contractions are mediated by the ET-A receptor and relaxations mediated by the ET-B receptor. The ET-B receptor mediated relaxation of human epicardial coronary arteries was endothelium-dependent.}},
  author       = {{Saetrum Opgaard, Ole}},
  keywords     = {{immunohistochemistry.; mRNA; receptors; ET-B; ET-A; endothelin; substance P; calcitonin gene-related peptide; vasoactive intestinal peptide; acetylcholine; NPY; ATP; noradrenaline; nerves; sensory; parasympathetic; sympathetic; veins; Coronary; arteries; Endocrinology; secreting systems; diabetology; Endokrinologi; sekretion; diabetologi; Cardiovascular system; Kardiovaskulära systemet}},
  language     = {{eng}},
  publisher    = {{Department of Internal Medcine, University Hospital of Lund,}},
  title        = {{Innervation and Functional Aspects of Neuropeptides in the Coronary Circulation.}},
  year         = {{1996}},
}