Atherosclerosis may be important in the modulation of arterial vasoreactivity and coronary artery flow. Since the endothelium is reduced or absent in atherosclerosis, drug effects are enhanced or modulated. To examine this hypothesis, vasoreactivity induced by serotonin (5-HT) was studied in isolated, perfused, and pharmacologically responsive normal and atherosclerotic human coronary arteries obtained within five hours post mortem. In this model, flow was maintained through the vessels and the effects of vasospasm and vasorelaxation on decreasing and increasing flow respectively were measured. Vessels 3 cm long and approximately 1.5 mm in internal diameter were dissected free and perfused at constant pressure (30 mm Hg) with oxygenated Krebs bicarbonate solution. 5-HT was introduced in the perfusate at 10(-5) M final concentration as a pulse of 100 ml followed by a 1-l washout with drug-free solution. Flow rate and total flow were measured. Normal and atherosclerotic coronary arteries showed peak reductions in flow rate of 22% and 92% respectively, while the times to peak reduction of flow averaged 6 and 4 min and the times to 50% relaxation averaged 13 and 24 min. Ultrasound imaging showed that heavily atherosclerotic regions with extensive focal plaque maintained the induced spasm for a longer period than regions with less disease within the same vessel. Silver nitrate staining showed that these heavily atherosclerotic regions were devoid of endothelium. Thus, atherosclerotic human coronary arteries show a larger magnitude of spasm which persists for a longer period of time as compared to normal coronaries.(ABSTRACT TRUNCATED AT 250 WORDS)