BACKGROUND: Coronary slow flow (CSF) is characterized by delayed opacification of coronary arteries in the absence of epicardial occlusive disease. In this study, we aimed to determine endothelin-1 (ET-1), nitric oxide (NOx) levels and time domain heart rate variability (HRV) parameters in patients with CSF and relationship among these parameters. METHODS: Thirty-three patients with CSF detected in the coronary angiography (17 females; mean age 55 +/- 7) and 19 patients with normal coronary flow (10 females; mean age 54 +/- 11) as a control group were enrolled in the study. Patients were divided into two groups according to exercise testing as if positive (group A, n = 8) or negative (group B, n = 25). RESULTS: Plasma ET-1 levels were higher in the group A patients (28.7 +/- 17.4 pg/ml) than that of group B (15.9 +/- 10.6 pg/ml) and control group (6.0 +/- 5.7 pg/ml); and higher in group B patients than that of control group (P < 0.05). Although groups A and B did not differ according to plasma NOx levels (23.4 +/- 13.5 micromol/L vs. 32.8 +/- 22.7 micromol/L, P > 0.05), NOx levels in group A were lower than the control group (23.4 +/- 13.5 micromol/L versus 42.5 +/- 15.9 micromol/L, P < 0.05). Time domain HRV parameters were decreased in all patient groups. This was more prominent in group A. Additionally, HRV parameters were negatively correlated with ET-1 and TIMI frame counts. TIMI frame count was also significantly correlated with ET-1 and NOx levels (r = 0.61, P < 0.0001, r =-0.30, P < 0.05). Upon intravascular ultrasonography investigation, the common finding was longitudinally extended massive calcification throughout the epicardial arteries. Mean intimal thickness was 0.50 +/- 0.13 mm (group A; 0.58 +/- 0.11 mm, group B 0.47 +/- 0.12 mm, P = 0.029). CONCLUSIONS: The present study demonstrated that in patients with CSF, both increased plasma ET-1, decreased plasma NOx and diffuse atherosclerosis may cause the decrease in HRV by effecting myocardial blood flow.