Impaired effect of endothelin-1 on coronary artery stiffness in type 2 diabetes Zenon S. Kyriakides a, * , Dimitrios Th. Kremastinos b , Athanasios E. Raptis b , Neil Johnston c , Sotirios A. Raptis b , David J. Webb c , Stamatis Kyrzopoulos d , Eftichia Sbarouni d a Red Cross Hospital, Athens, Greece, 2nd Cardiology Department, University of Athens, School of Medicine, University General Hospital ‘‘Attikon’’, Athens, Greece b 2nd Department of Internal Medicine- Propaedeutic, Research Institute and Diabetes Center, University of Athens, School of Medicine, University General Hospital ‘‘Attikon’’, Athens, Greece c University of Edinburgh, Western General Hospital, UK d Onassis Cardiac Center, Athens, Greece Received 13 June 2005; received in revised form 4 August 2005; accepted 18 September 2005 Available online 2 December 2005 Abstract Aim: We examined whether there is a differential effect of endothelin-A antagonism on coronary artery compliance in type 2 diabetes mellitus compared to non-diabetic patients. Patient and methods: We examined 32 patients, 11 type 2 diabetes mellitus and 21 non-diabetic patients, with atherosclerotic epicardial arteries free of significant luminal stenoses. Intracoronary BQ-123 (6 Amol), an endothelin-A receptor antagonist, was infused over 20 min. The artery lumen area in the proximal arterial segment was measured at end diastole and end systole before and after BQ-123 administration using an intravascular ultrasound catheter. Calculations were made of normalized arterial compliance index, in mm Hg À 1 Â10 3 and of arterial stiffness index h. Results: Pulse pressure and heart rate did not change after BQ-123. In type 2 diabetes mellitus, normalized compliance index decreased from 1.79 T 1.36 at baseline to 1.29 T 0.82 after BQ-123 administration, whereas in non-diabetic patients it increased from 2.10 T 1.36 to 3.00 T 2.07 ( p < 0.05 versus baseline) ( F = 6.39, p = 0.02). In type 2 diabetes mellitus, b index increased from 1.97 T 0.53 to 2.46 T 0.95, whereas in non- diabetic patients it decreased from 1.83 T 0.95 to 1.63 T 0.84 ( F = 7.80, p = 0.009). Big endothelin-1 at baseline was correlated with the baseline b index ( p < 0.0001, r = 0.68). Conclusions: Big endothelin-1 is correlated with the coronary artery stiffness. The effect of endogenous endothelin-1 on coronary artery stiffness is impaired in type 2 diabetes mellitus. This may have important therapeutic implications with respect to the introduction of endothelin receptor antagonists as cardiovascular therapeutic agents. D 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Endothelin; Artery elasticity; Catheterization; Type 2 diabetes mellitus 1. Introduction Endogenous production of endothelin-1 contributes to the maintenance of coronary vascular tone in coronary artery disease and healthy controls [1]. In animal models of diabetes reduced responsiveness to endothelin-1 is seen in both the large vessels and the microvasculature [2,3]. In addition, exogenous as well as endogenous endothelin-1 exerts impaired vasoconstriction, in forearm arteries, in patients with type 2 diabetes mellitus [4,5]. Compensatory vessel enlargement occurs to a greater degree in patients with unstable than with stable coronary syndromes, and is associated with increased coronary artery distensibility 0167-5273/$ - see front matter D 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2005.09.018 * Corresponding author. B Cardiology Department Red Cross Hospital, 1 Erythrou Stavrou str., Athens 115 26, Greece. Tel.: +30 210 6414 705, 6414 587, 8104 554; fax: +30 210 6414 587. E-mail address: zskyr@otenet.gr (Z.S. Kyriakides). International Journal of Cardiology 112 (2006) 207 – 212 www.elsevier.com/locate/ijcard