title: ACE inhibitors and statins acutely improve endothelial dysfunction of human coronary arterioles.
abstract: Long-term treatment with angiotensin-converting enzyme (ACE) inhibitors as well as angiotensin II type 1 (AT(1)) 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 (AT(1) 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, respectively). 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.
authors.affiliation: Department of Cardiology, University of Heidelberg, 69115 Heidelberg, Germany. ctiefenbacher@med.uni-heidelberg.de
authors.forename: Christiane P
authors.initials: CP
authors.lastname: Tiefenbacher
authors.forename: Stefanie
authors.initials: S
authors.lastname: Friedrich
authors.forename: Tina
authors.initials: T
authors.lastname: Bleeke
authors.forename: Christian
authors.initials: C
authors.lastname: Vahl
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Chen
authors.forename: Feraydoon
authors.initials: F
authors.lastname: Niroomand
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001160:Arterioles / Q000187:drug effects; D001161:Arteriosclerosis / Q000188:drug therapy / Q000503:physiopathology; D001562:Benzimidazoles / Q000627:therapeutic use; D001713:Biphenyl Compounds; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology; D003331:Coronary Vessels / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use; D005260:Female; D000077340:Fluvastatin; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007211:Indoles / Q000627:therapeutic use; D017706:Lisinopril / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D009599:Nitroprusside / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013777:Tetrazoles / Q000627:therapeutic use; D014652:Vascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D013777:Tetrazoles; D014665:Vasodilator Agents; D009599:Nitroprusside; D012701:Serotonin; D000077340:Fluvastatin; D006632:Histamine; D017706:Lisinopril; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D000109:Acetylcholine; C081643:candesartan; D019331:NG-Nitroarginine Methyl Ester