Selective endothelin A-receptor blockade attenuates coronary microvascular dysfunction after coronary stenting in patients with type 2 diabetes.
BACKGROUND
Endothelin-1 may be involved in the development of diabetic microangiopathy. We studied the effect of endothelin-1 blockade on myocardial microcirculation during coronary stenting.


METHODS
Patients with type 2 diabetes and stable coronary artery disease undergoing elective percutaneous coronary intervention (PCI) were randomized to bolus dose of 500 mg bosentan (n = 4), a dual endothelin receptor blocker, or intracoronary administration of 0.03 mmol BQ123 (n = 6), a selective endothelin A-receptor blocker, or placebo (n = 5), respectively. Coronary flow reserve (CFR) was measured immediately post-PCI. CFR was also measured in five nondiabetic controls post-coronary stenting.


RESULTS
Patients in the placebo group had (P < 0.05) lower values of CFR (2.3 +/- 1.2) as compared to those who received endothelin blockade (n = 10; 3.1 +/- 0.7) and nondiabetic controls (4.9 +/- 2.3). Patients who received BQ123 showed significantly higher CFR (3.3 +/- 0.5; P < 0.05) as compared to those on placebo. Nondiabetic patients had significantly higher CFR as compared to patients with diabetes (4.9 +/- 2.3 and 2.8 +/- 1.0, respectively; P < 0.05).


CONCLUSIONS
Coronary microvascular dysfunction is present during coronary stenting in patients with type 2 diabetes and may be reversed by selective endothelin A-receptor blockade. Targeting endothelin system may be of importance in protecting the myocardium against ischemic events during elective PCI in type 2 diabetic patients.
Papadogeorgos
Nikolaos Ostlund
NO
Karolinska Institute, Department of Clinical Sciences, Department of Cardiology, Danderyd Hospital, Stockholm, Sweden.
Bengtsson
Mattias
M
Kalani
Majid
M
D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation*; D000077300:Bosentan; D003324:Coronary Artery Disease / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D003326:Coronary Circulation / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D065130:Endothelin A Receptor Antagonists; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D010456:Peptides, Cyclic / Q000008:administration & dosage*; D044022:Receptor, Endothelin A / Q000378:metabolism; D015607:Stents; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome
D065130:Endothelin A Receptor Antagonists; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D013449:Sulfonamides; D000077300:Bosentan; C072247:cyclo(Trp-Asp-Pro-Val-Leu)