Endothelin-1 is not involved in serotonin-induced coronary spasm in a swine model.
OBJECTIVE
The role of endothelin-1 (ET-1) in the pathogenesis of coronary artery spasm is not well understood. We aimed to determine if ET-1 is involved in serotonin-induced coronary spasm in the swine model.


METHODS
In 10 miniature pigs, a segment of the left anterior descending coronary artery was denuded and irradiated with X-ray. Three months after endothelial denudation, coronary vasomotion was assessed in vivo by quantitative arteriography.


RESULTS
Intracoronary serotonin at 10 micrograms/kg provoked coronary spasm (augmented narrowing of the luminal diameter) at the denuded site (diameter reduction 93 +/- 4%) but not at the non-denuded control site (19 +/- 4%, P < 0.01) associated with ST segment elevation in the region perfused by the denuded artery. Intracoronary administration of ET-1 at 25 ng/kg caused mild vasoconstriction of the denuded (26 +/- 4) and non-denuded site (16 +/- 3%, n.s.), but provoked ST segment elevation in the regions perfused by both the denuded and non-denuded arteries. The treatment with an endothelin antagonist (BQ123 0.1 mg/kg) significantly attenuated coronary vasoconstriction and ST segment elevation evoked with ET-1, but did not alter serotonin-induced vasoconstriction either at the denuded or control site.


CONCLUSIONS
The results of this study suggest that endogenous ET-1 may not be involved in the pathogenesis of serotonin-induced coronary spasm in our swine model.
Fukai
T
T
Research Institute of Angiocardiology, Kyushu University School of Medicine, Fukuoka, Japan.
Egashira
K
K
Numaguchi
K
K
Hata
H
H
Takahashi
T
T
Kasuya
H
H
Sakata
M
M
Shimokawa
H
H
Takeshita
A
A
D000818:Animals; D017023:Coronary Angiography; D003329:Coronary Vasospasm / Q000097:blood / Q000209:etiology* / Q000473:pathology; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000097:blood / Q000494:pharmacology*; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D013552:Swine; D013556:Swine, Miniature; D014661:Vasoconstriction / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; D012701:Serotonin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)