The effects of atrial natriuretic peptide (ANP) on transmural myocardial blood flow distribution and the reactive hyperemic response in the presence and absence of flow-limiting coronary stenosis were examined in chronically instrumented conscious dogs. Ten-second coronary occlusion without subsequent flow restriction resulted in marked reactive hyperemic responses (Doppler flow probes), mean flow debt repayment was 481±55percent;. When the 10-second coronary occlusions were followed by a 20-second partial restriction that allowed normal preocclusion coronary inflow, the subsequent reactive hyperemia was significantly augmented, mean flow debt repayment was 938±91percent; (p<0.05). Pretreatment with ANP (3μg/kg) did not alter the flow debt repayment after a 10-second occlusion without restriction (474±30percent;, NS) but attenuated the augmentation of reactive hyperemia resulting from the 20-second inflow restriction, flow debt repayment (613±±66percent;, NS). Regional myocardial blood flow to the ischemic region was measured during restricted inflow after a 10-second coronary occlusion before and after ANP pretreatment. Before ANP, subendocardial flow decreased (0.54±0.04 ml/min/g) and subepicardial flow significantly increased (1.03±0.12 ml/min/g) when compared with the nonischemk zone (subendocardial, 1.03±0.09 ml/min/g; subepicardial, 0.87±0.09 ml/ min/g, p<0.05), indicating maldistribution of the restricted inflow. The resultant subendocardial-to-subepicardial ratio in the ischemic region was significantly decreased when compared with the nonischemic region (0.56±0.03 vs. 1.18±0.04, p<0.05). After ANP pretreatment, subendocardial flow to the ischemic region significantly increased (0.71±0.07 ml/min/g, p<0.05) and the subendocardial-to-subepicardial ratio in the ischemic zone was significantly unproved (0.91±0.10, p<0.05). Myocardial flow measured daring coronary occlusion was not altered after ANP pretreatment, indicating no change in native collateral flow to the ischemic region. Myocardial oxygen consumption, aortic and left ventricular end-diastolic pressures, dP/dt, and heart rates were also not affected by pretreatment with ANP. These data indicate that ANP favorably redistributed blood flow to the subendocardium and reduced subendocardial ischemia after a transient occlusion in the presence of a flow limiting coronary stenosis. The reversal of subendocardial hypoperfusion by ANP hi the absence of alterations of intrinsic vascular reactivity or native collateral flow supports a dilation effect of ANP on the intramural arteries.