Effect of low dose infusions of ile-atrial natriuretic peptide in healthy elderly males: evidence for a postreceptor defect.

Low dose infusions of atrial natriuretic peptide (ANP) have significant biological effects in young adults. In view of the accumulating evidence of age-related changes in ANP physiology, we investigated the effects of a 2-h low dose infusion of ile12-ANP (1.5 pmol/kg/min) in eight healthy, supine, normotensive elderly men in a single blind, random order, placebo-controlled study. Calculated MCR of ANP was 3.3 +/- 0.4 L/min, disappearance half-life 4.1 +/- 0.4 min, and volume of distribution 21 +/- 4 L. The ile-ANP infusions induced the expected significant (3-fold) increases in plasma ANP immunoreactivity in association with enhancement of both plasma and urine cyclic guanosine monophosphate. Despite this, there were no measurable natriuretic effects or changes in blood pressure, and the activities of the renin-angiotensin-aldosterone and sympathetic nervous systems were unchanged. These findings suggest an abnormality in the post-cyclic guanosine monophosphate effector of ANP among elderly normotensive men.