Long-term treatment with 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 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 endotheliumdependent agonists (histamine, serotonin and acetylcholine) as well as to the endotheliumindependent agonist sodium nitroprusside (SNP) were investigated under baseline conditions and following incubation (15min) with lisinopril (ACE-inhibitor), candesartan (AT(1) receptor antagonist) or fluvastatin. In atherosclerotic vessels vasorelaxation was significantly reduced to all endotheliumdependent agonists, however not to SNP (77±8, -24±16, -46±24 and 98]±8% relaxation for histamine, serotonin, acetylcholine and sodium nitroprusside, respectively). Lisinopril and fluvastatin but not candesartan, significantly improved the responses to the endotheliumdependent agonists (lisinopril: 94±4, 17±22, -20 ±13%; fluvastatin: 96±8, 2±21, -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 (DCI), an inhibitor of kinine-forming enzymes. Pretreatment with a 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 ACEinhibitors and statins via increasing the availability of NO.