Modulation of serotonin-induced vasospasm by endothelium and monoamine oxidase.
Endothelial modulation of flow induced by intraluminal serotonin (5-HT) in isolated and perfused bovine coronary artery segments was studied. A constant-pressure continuous perfusion apparatus was utilized. Control coronary arteries were perfused with a fixed volume of serotonin-containing solution followed by a serotonin-free solution, and flow-rate changes during onset and relaxation of vasospasm were measured. Both monoamine oxidase inhibition by iproniazide and endothelium disruption by collagenase increased the rate of onset and magnitude of vasospasm. When the endothelium was intact the vasospasm continued to increase, reaching maximum well after the end of the serotonin perfusion, followed by slow relaxation toward baseline. This contrasted with de-endothelialized vessels in which the increase in contractile response terminated abruptly at the end of the serotonin perfusion and returned rapidly to baseline. Coronary arteries stimulated with prostaglandin F2 alpha responded similarly to de-endothelialized vessels stimulated by 5-HT, although further de-endothelialization of F2 alpha-stimulated vessels showed increased rates of onset and relaxation of vasospasm, suggesting a physical barrier role for the endothelium towards unmetabolized agents. These observations are consistent with the hypothesis that endothelial cells are capable of taking up, storing and subsequently releasing serotonin. The results suggest a protective role of the endothelium as a metabolic and physical barrier. This may represent an anatomical substrate favouring the development of localized vasospasm at sites where the endothelium is injured.
Morcos
N C
NC
Department of Medicine, University of California, Irvine 92717.
Grandaw
P P
PP
Henry
W L
WL
Purdy
R E
RE
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D008995:Monoamine Oxidase / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D012701:Serotonin; D008995:Monoamine Oxidase