CHRONIC STIMULATION OF ATRIAL-NATRIURETIC-PEPTIDE ATTENUATES THE SECRETORY RESPONSE TO POSTURAL CHANGES

Atrial natriuretic peptide (ANP), released upon pulmonary vasoconstric tion, modulates pulmonary vascular tone through an increase of cellula r guanosine 3',5'-cyclic monophosphate. In patients with cardiopulmona ry disease, however, the plasma levels of ANP are relatively low, cons idering the high pulmonary arterial pressure. To evaluate the release mechanism of the hormone, plasma ANP levels were studied by the manipu lation of right atrial stretch with different body postures. In health y young subjects, the plasma ANP concentration significantly increased when posture changed from an upright to a supine position (p < 0.01). In contrast, plasma ANP concentrations were significantly higher in p atients with chronic obstructive pulmonary disease and elderly subject s (p < 0.01), but the plasma levels did not increase upon the change i n posture. Consistent with in vitro findings, the data indicate that c hronic ANP stimulation attenuates the secretory response to acute stim uli. In addition, it was demonstrated that the ratio of guanosine 3',5 '-cyclic monophosphate to ANP, reflecting the biologic effect of the h ormone, was significantly lower in patients with chronic obstructive p ulmonary disease as well as in the elderly (p < 0.05). This decreased biologic activity aggravated the blunted ANP response and may contribu te to the development of pulmonary hypertension.