Endothelin receptor blockade improves endothelial function in atherosclerotic patients on angiotensin converting enzyme inhibition.
OBJECTIVE
Endothelin-1 (ET-1) and angiotensin II may contribute to endothelial dysfunction, which is associated with increased risk of events in patients with coronary artery disease. The objective was to test whether dual ETA/ETB receptor antagonism improves endothelium-dependent vasodilatation (EDV) in atherosclerotic patients, also on treatment with angiotensin converting enzyme (ACE) inhibitor.


METHODS
EDV and endothelium-independent vasodilatation were determined in 37 patients with atherosclerosis during measurement of forearm blood flow (FBF) with venous occlusion plethysmography. The patients were then randomized to treatment with ramipril 10 mg o.d. (n=21) or placebo (n=16) for 3 months in a double-blind fashion.


RESULTS
Intra-arterial infusion of the ETA receptor antagonist BQ123 and the ETB receptor antagonist BQ788 (both 10 nmol min(-1)) increased basal FBF by 42 +/- 4% (P <0.001) and enhanced EDV (P <0.001). Following 3 months ramipril treatment, ET receptor blockade still enhanced EDV. Acetylcholine 10 and 30 mg min(-1) increased FBF by 68 +/- 12 and 64 +/- 12 mL min(-1)/1000 mL before vs. 101 +/- 17 and 101 +/- 16 mL min(-1)/1000 mL following ET receptor blockade in the ramipril group (P <0.001).


CONCLUSIONS
Dual ETA/ETB receptor blockade improves endothelial function and exerts direct vasodilator effects in patients with atherosclerosis, also on treatment with ramipril suggesting that ET receptor blockade may have important therapeutic effects when added to ACE inhibition in these patients.
Böhm
F
F
Department of Cardiology, Karolinska University Hospital, Solna, Stockholm, Sweden. felix.bohm@medks.ki.se
Beltran
E
E
Pernow
J
J
D000109:Acetylcholine / Q000008:administration & dosage; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage; D010456:Peptides, Cyclic / Q000008:administration & dosage; D010880:Piperidines / Q000008:administration & dosage; D010991:Plethysmography / Q000379:methods; D017257:Ramipril / Q000627:therapeutic use; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D015415:Biomarkers; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D014665:Vasodilator Agents; C086539:BQ 788; D017257:Ramipril; D000109:Acetylcholine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)