OBJECTIVE Iodinated contrast media can cause a number of well-described acute hemodynamic and vascular effects including vascular spasm, hypotension, and arrhythmias. Coronary microvessels were studied in vitro after high-dose exposure to an ionic, high-osmolar contrast agent diatrizoate meglumine in vivo. The aim of this study was to examine the endothelium-dependent and endothelium-independent vasodilator responses of the microvessels after previous contrast media administration in a clinically relevant setting. METHODS Left coronary angiography was performed on six pigs using a cumulative dose of 60 mL (5 mL/injection) of diatrizoate meglumine. After 1 hour of reperfusion, epicardial coronary microvessels were studied in vitro in a pressurized, no-flow state with video microscopy. The vasodilators bradykinin, calcium ionophore A23187, and sodium nitroprusside were sequentially applied extraluminally after preconstriction. Serotonin and the thromboxane A2 analog U46619 were studied without preconstriction. RESULTS Microvessels exposed to diatrizoate meglumine had normal relaxation responses to the endothelium-dependent vasodilators bradykinin and calcium ionophore A23187 when compared to control vessels. The vasoconstrictor responses to U46619 and serotonin were not significantly altered compared to control vessels. Responses to the endothelium-independent vasodilator sodium nitroprusside were not reduced or were slightly enhanced after exposure to contrast media. CONCLUSIONS Coronary resistance vessels responses to the endothelium-dependent vasodilators bradykinin and calcium ionophore A23187 are not diminished after previous exposure to diatrizoate meglumine. The vasoconstrictor responses to U46619 and serotonin were similarly unaffected by previous exposure to contrast media. This suggests that, when used in clinically relevant amounts, diatrizoate meglumine does not cause functional endothelium or vascular smooth muscle impairment.