Preventive effect of chronic endothelin type A receptor antagonist on coronary microvascular spasm induced by repeated epicardial coronary artery endothelial denudation in pigs.
OBJECTIVE
We investigated the role of endothelin-1 (ET-1) in coronary microvascular spasm in a porcine model.


METHODS
A flowmeter was implanted around the left anterior descending coronary artery (LAD), and epicardial coronary artery endothelial denudation (ED) was performed just distal to the flowmeter every 2 weeks (W) until 6 W in 10 pigs (ED group). Ten pigs were chronically treated with endothelin type A receptor (ET(A)) antagonist (TA-0201, 0.1 mg/kg/day, ED+ET(A) group), while neither ED nor administration of ET(A) antagonist was performed in 12 pigs (Control group). We assessed changes in LAD blood flow and the denuded site diameter induced by acetylcholine (ACh, 0.05 microg/kg i.c.).


RESULTS
In the ED group, administration of ACh to LAD induced zero flow without LAD diameter reduction at 8 W. In the ED+ET(A) group, the decrease in LAD blood flow response to ACh was suppressed. Chronic administration of TA-0201 suppressed ROS generation in the myocardium. Decreases of eNOS and intimal thickening were smaller in the TA-0201 administration group than the non-TA-0201 administration group.


CONCLUSIONS
Chronic administration of ET(A) receptor antagonist is effective to prevent coronary microvascular spasm.
Osugi
Taku
T
First Department of Internal Medicine, Fukushima Medical University, Fukushima 960-1295, Japan.
Saitoh
Shu-ichi
S
Matumoto
Ken
K
Muto
Mituru
M
Aikawa
Kazuhiko
K
Ohkawara
Hiroshi
H
Sugimoto
Kouichi
K
Kamioka
Masashi
M
Ishibashi
Toshiyuki
T
Maruyama
Yukio
Y
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001835:Body Weight; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D054326:Coronary Sinus / Q000378:metabolism; D003329:Coronary Vasospasm / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D034421:Sus scrofa; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D011743:Pyrimidines; D017382:Reactive Oxygen Species; D044022:Receptor, Endothelin A; D013449:Sulfonamides; C113972:T 0201; D014665:Vasodilator Agents; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine