Endothelial vasodilator function is preserved at the spastic/inflammatory coronary lesions in pigs.
BACKGROUND
The question of whether or not endothelial vasodilator function in the spastic coronary artery is preserved is still controversial. We recently developed a porcine model in which long-term and local treatment with interleukin-1beta (IL-1beta) from the adventitial site causes coronary arteriosclerotic changes and vasospastic responses to autacoids. The aim of this study was to examine the endothelial vasodilator function in our new porcine model of the spasm both in vivo and in vitro.


RESULTS
A segment of the porcine coronary artery was aseptically wrapped with cotton mesh that held absorbed IL-1beta-bound microbeads. Two weeks after the procedure, intracoronary administration of serotonin caused coronary vasospasm at the IL-1beta-treated site (n = 10). Coronary vasodilatation to bradykinin, substance P, or an increase in coronary blood flow was preserved at the spastic site. Vasodilator responses to 3-morpholinosydnonimine (an NO donor) and nitroglycerin also were comparable between the 2 sites. The vasoconstricting response to N(G)-monomethyl-L-arginine and the extent of the augmentation of the serotonin-induced vasoconstriction were comparable between the 2 sites. Organ chamber experiments showed that endothelium-dependent relaxations to bradykinin, the calcium ionophore A23187, and even the vasospastic agonist serotonin were preserved at the spastic site, whereas contractions to serotonin were augmented at the spastic site regardless of the presence or absence of the endothelium (n = 6). Endothelium-independent relaxations to sodium nitroprusside were also preserved at the spastic site.


CONCLUSIONS
These results indicate that endothelial vasodilator function is preserved at the spastic site and that the spasm is caused primarily by smooth muscle hypercontraction in our porcine model.
Miyata
K
K
Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka, Japan.
Shimokawa
H
H
Yamawaki
T
T
Kunihiro
I
I
Zhou
X
X
Higo
T
T
Tanaka
E
E
Katsumata
N
N
Egashira
K
K
Takeshita
A
A
D000818:Animals; D003329:Coronary Vasospasm / Q000139:chemically induced / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D007375:Interleukin-1; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D009205:Myocarditis / Q000503:physiopathology*; D012701:Serotonin; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
D007375:Interleukin-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D012701:Serotonin