HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 286/4/H1425    most recent 00783.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Tiefenbacher, C. P. Articles by Niroomand, F. Search for Related Content PubMed PubMed Citation Articles by Tiefenbacher, C. P. Articles by Niroomand, F.

ACE inhibitors and statins acutely improve endothelial dysfunction of human coronary arterioles

¹Department of Cardiology, University of Heidelberg, 69115 Heidelberg; and ²Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany

Submitted 14 August 2003 ; accepted in final form 20 November 2003

Long-term treatment with angiotensin-converting enzyme (ACE) inhibitors as well as angiotensin II type 1 (AT₁) receptor antagonists and statins reduces cardiovascular mortality in patients with coronary artery disease as well as chronic heart failure. Little is known about the acute effects of these compounds on vascular reactivity of coronary resistance vessels. Coronary arterioles were obtained from patients undergoing coronary bypass operation (atherosclerosis group) or valve replacement (control group). Responses to endothelium-dependent agonists (histamine, serotonin, and acetylcholine) as well as to the endothelium-independent agonist sodium nitroprusside (SNP) were investigated under baseline conditions and after incubation (15 min) with lisinopril (ACE inhibitor), candesartan (AT₁ receptor antagonist), or fluvastatin. In atherosclerotic vessels, vasorelaxation was significantly reduced to all endothelium-dependent agonists but not, however, to SNP (77 ± 8, –24 ± 16, –46 ± 24, and 98 ± 8% relaxation for histamine, serotonin, acetylcholine, and SNP, respectively). Lisinopril and fluvastatin but not candesartan significantly improved the responses to the endothelium-dependent agonists (lisinopril: 94 ± 4, 17 ± 22, and –20 ± 13%; fluvastatin: 96 ± 8, 23 ± 21, and –25 ± 18% relaxation for histamine, serotonin, and acetylcholine, repectively). The effect of lisinopril was prevented by pretreatment with a bradykinin antagonist (HOE-130) and dichloroisocoumarine, an inhibitor of kinine-forming enzymes. Pretreatment with a nitric oxide (NO) synthase inhibitor abolished the improvement of endothelial function by lisinopril and fluvastatin. Vascular reactivity in the control group was not influenced by any of the pharmacological interventions. The data demonstrate that in atherosclerosis, endothelium-dependent relaxation of coronary resistance arteries is severely compromised. The impairment can acutely be reversed by ACE inhibitors and statins via increasing the availability of NO.

nitric oxide; atherosclerosis; vasoconstriction/relaxation; angiotensin-converting enzyme inhibitors

This article has been cited by other articles:

				K. Denk, J. Albers, N. Kayhan, D. Ister, A. Bonz, C. Werner, T. Munzel, and C.-F. Vahl Evidence for a negative inotropic effect of obesity in human myocardium? Eur. J. Cardiothorac. Surg., August 1, 2009; 36(2): 300 - 305. [Abstract] [Full Text] [PDF]

				A. Schafer, D. Fraccarollo, M. Eigenthaler, P. Tas, A. Firnschild, S. Frantz, G. Ertl, and J. Bauersachs Rosuvastatin Reduces Platelet Activation in Heart Failure: Role of NO Bioavailability Arterioscler Thromb Vasc Biol, May 1, 2005; 25(5): 1071 - 1077. [Abstract] [Full Text] [PDF]

				P. H. Stone, D. M. Lloyd-Jones, S. Kinlay, B. Frei, W. Carlson, J. Rubenstein, T. C. Andrews, M. Johnstone, G. Sopko, H. Cole, et al. Effect of Intensive Lipid Lowering, With or Without Antioxidant Vitamins, Compared With Moderate Lipid Lowering on Myocardial Ischemia in Patients With Stable Coronary Artery Disease: The Vascular Basis for the Treatment of Myocardial Ischemia Study Circulation, April 12, 2005; 111(14): 1747 - 1755. [Abstract] [Full Text] [PDF]