To study whether the release of atrial natriuretic factor (ANF) was altered in diabetic cardiac autonomic neuropathy (CAN), we determined plasma ANF concentrations during exercise and changes of posture in three groups of age- and sex-matched subjects(9 healthy subjects, 7 diabetic patients with CAN, and 7 diabetic patients without CAN). During exercise, plasma ANF concentrations rose threefold (P < .001), and this increase was similar in the three groups. However, heart-rate response to exercise was impaired in the two groups of diabetic patients (P < .004 vs. healthy subjects) but was more severely impaired in patients with CAN (P < .03 vs. patients without CAN). In healthy subjects and patients without CAN, the increases of ANF during exercise correlated significantly with those of heart rate, systolic blood pressure, and rate-pressure product (P < .01). In patients with CAN, the correlation was found exclusively with heart rate (P < .01). An increase of ventricular ejection fraction occurred in all groups (P < .001) but without showing statistical differences between groups. After 30 min of standing, a similar postural drop of plasma ANF concentrations (P < .002) was observed in all subjects, reflecting preserved sympathetic control of vessels. In conclusion, exercise induces an increase of plasma ANF in diabetic patients with CAN. This increase, occurring similarly to healthy subjects, indicates that autonomic activation plays a minor role in ANF release during exercise. Impaired heart-rate response to exercise in patients without CAN suggests early damage of autonomic function, undetected by conventional rest tests.

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