In vivo demonstration of enhanced arterial constrictor response to serotonin following focal endothelial cell loss.
Arterial sensitivity to vasospasm was assessed prior to and 2 weeks following a 15-min period of external compression of the superficial femoral artery in dogs. Compression was achieved by placing a plastic cuff around the artery to produce a 40-60% reduction in the artery cross-sectional area. An additional six dogs were used to assess morphologic changes produced in the artery immediately and at 2 weeks after compression. Angiography following intraarterial infusions of serotonin (10 and 30 micrograms/min), norepinephrine (0.1 microgram/min), ergonovine (20 micrograms/min), and the thromboxane mimic U-46,619 (0.1 microgram/min) demonstrated a specific sensitivity to serotonin 2 weeks after the 15-min application of external arterial compression. The serotonin response was antagonized by the specific serotonin (5-HT2) receptor antagonist, ketanserin. Scanning electron microscopy of the acutely injured luminal surface revealed loss of endothelium and deposition of platelets. Patchy areas with intact endothelium and migrating leukocytes were located within the denuded sites. Two weeks after constrictor placement, the compressed area appeared as a raised or semiraised lesion in which the orientation and shape of the luminal cells were distinctly delineated from the adjacent noninjured segments. However, the luminal cells appeared to be endothelium that had regrown over the previously denuded area. The results of this study demonstrate, in an in vivo model, an enhancement in serotonin-mediated vasoconstriction following intimal injury and repair and support the suggestion that endothelial damage or dysfunction may play a role in the pathophysiology of arterial spasm.
Orlandi
C
C
Cardiovascular Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
Humphrey
W R
WR
Hollenberg
N K
NK
Schaub
R G
RG
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology*; D004874:Ergonovine / Q000494:pharmacology; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D008855:Microscopy, Electron, Scanning; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009638:Norepinephrine / Q000494:pharmacology; D011312:Pressure; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D011450:Prostaglandin Endoperoxides, Synthetic; D012701:Serotonin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D004874:Ergonovine; D009638:Norepinephrine