Influence of age and dose on the end-organ responses to atrial natriuretic peptide in humans.
To test the hypothesis that age differentially affects the natriuretic, hemodynamic, and humoral response to exogenous ANP, we studied seven young (Y, 20 to 39 years) and five old (O, 65 to 83 years) healthy, normotensive, nonobese men during infusion of synthetic human ANP1,28 at two different rates: 1) 0.05 microgram/kg/min (high dose) for 1 h and 2) 0.005 microgram/kg/min (low dose) for 1 h. Compared to young, the old had higher basal ANP levels (O = 142 +/- 41 v Y = 29 +/- 4 pmol/L, P less than .025), achieved higher plasma levels with low-dose infusion (O = 327 +/- 24 v Y = 155 +/- 37 pmol/L, P less than .001) and had a longer ANP half-life (O = 7.8 +/- 0.6 v Y = 4.3 +/- 0.6 min, P less than .001), suggesting decreased catabolism in the old compared to the young. Despite these age-related differences in ANP levels, there was no difference in urinary sodium or cyclic GMP excretion. After termination of the low-dose infusion, plasma ANP and urinary cGMP promptly returned to baseline levels. Despite this, a sustained natriuresis (2-fold above control) was observed for 3 h in both groups. Low-dose infusion was associated with sustained suppression of aldosterone with minimal hemodynamic changes. During high-dose infusions there was no difference in natriuresis or peak ANP levels between the two groups (O = 1299 +/- 93 v Y = 1140 +/- 54 pmol/L). In contrast to the low-dose infusion, the high-dose infusion produced a transient natriuresis lasting only for the duration of the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Clark
B A
BA
Charles A. Dana Research Institute, Harvard-Thorndike Laboratory, Beth Israel Hospital, Boston, Massachusetts.
Elahi
D
D
Shannon
R P
RP
Wei
J Y
JY
Epstein
F H
FH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000502:physiology*; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D006152:Cyclic GMP / Q000652:urine; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood; D012964:Sodium / Q000652:urine; D013997:Time Factors
D009320:Atrial Natriuretic Factor; D012964:Sodium; D006152:Cyclic GMP; D009638:Norepinephrine