Intracoronary endothelin receptor blockade improves endothelial function in patients with coronary artery disease.
Endothelin (ET)-1 receptor blockade improves endothelial function in the forearm of patients with atherosclerosis. The aim was to investigate whether intracoronary ET receptor blockade improves coronary endothelial function and increases blood flow in patients with coronary artery disease. Ten patients received a 60-minute infusion of either the selective ETA receptor antagonist BQ123 (40 nmol/min, n = 6) or BQ123 + the ETB receptor antagonist BQ788 (40 nmol/min, n = 4). In all patients, substance P, an endothelium-dependent vasodilator, did not increase baseline coronary flow reserve with thermodilution (CFRThermo) (0.71 +/- 0.14 s during NaCl versus 0.59 +/- 0.14 s during substance P) or baseline quantitative coronary angiography (QCA) (2.74 +/- 0.16 mm versus 2.83 +/- 0.20 mm). After ET receptor blockade, however, the response to substance P was significantly improved as determined both by CFRThermo (0.62 +/- 0.14 s during NaCl versus 0.48 +/- 0.10 s during substance P, p < 0.05) and by QCA (2.70 +/- 0.18 mm versus 2.85 +/- 0.19 mm, p < 0.05). In addition, ET blockade increased blood flow in all patients by 16% +/- 10% (n = 10, p < 0.05) and in the BQ123 group by 22% +/- 16% (n = 6, p < 0.05). Furthermore, ETA blockade increased blood flow significantly more than did dual ETA/ETB blockade (p < 0.05). These findings indicate that ET receptor blockade may be a new therapeutic strategy to improve coronary vascular function in patients with coronary artery disease.
Böhm
Felix
F
Department of Cardiology, Karolinska Institutet and Karolinska University Hospital, Solna, S-171 76 Stockholm, Sweden. felix.bohm@ki.se
Jensen
Jens
J
Svane
Bertil
B
Settergren
Magnus
M
Pernow
John
J
D000368:Aged; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D050197:Atherosclerosis / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D002196:Capillaries / Q000502:physiology; D006328:Cardiac Catheterization; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000503:physiopathology*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology*; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology
D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D008055:Lipids; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; C086539:BQ 788; D002097:C-Reactive Protein; C072247:cyclo(Trp-Asp-Pro-Val-Leu)