Evidence That Atrial Natriuretic Peptide Tissue Extraction Is Not Changed by Large Increases in Its Plasma Levels Induced by Pacing in Humans
G. Iervasi,
A. Clerico,
A. Pilo,
F. Vitek,
S. Berti,
C. Palmieri,
M. Ravani,
L. Sabatino,
C. Manfredi,
M. G. Del Chicca,
A. Biagini and
L. Donato
Laboratory of Cardiovascular Endocrinology, CNR Institute of
Clinical Physiology, Pisa, Italy; and the Institute of Biophysics,
First Medical Faculty, Charles University (F.V.), Prague, Czech
Republic
Address all correspondence and requests for reprints to: G. Iervasi, M.D., CNR Institute of Clinical Physiology, Via Savi 8, 56100 Pisa, Italy. E-mail: iervasi{at}nsifc.ifc.pi.cnr.it (Dr. Giorgio
Atrial natiurectic peptide (ANP) is a cardiac hormone with avery short
plasma half-life, which plays an important role ina variety of
clinical conditions associated with an increasein pressure and/or
volume overload on the heart. The MCR ofthe hormone is considered to
represent a stable parameter, reflectingthe uptake and degradation
rate of ANP by the periphery, onlyscarcely affected by rapid
oscillations of circulating levels.To evaluate the extent to which MCR
is affected by rapid andlarge variations of circulating levels of the
hormone, we measuredMCR in five patients with different degrees of
myocardial function(from normal to severely impaired), in whom changes
in ANP levelswere induced by atrial and/or ventricular pacing. Cardiac
outputwas simultaneously measured by thermodilution to calculate whole
bodyextraction of ANP. During constant iv infusion of
[125I]ANP,the hormone MCR was determined both under
basal conditions (attracer equilibration, 20–30 min after the start
of infusion)and during atrial and ventricular pacing. Pacing
maneuvers,begun 50 min after the start of infusion, induced a marked
andrapid increase in endogenous plasma ANP values in all patients(on
the average, 3.7-fold compared to basal values; range, 1.8–5.68),
whereascorresponding values of [125I]ANP only minimally
changed. TheMCR of ANP (3.62 ± 1.06 L/min, mean ±
SD) slightlydecreased (by repeated measures ANOVA,
P = 0.0458) during atrialand ventricular pacing
procedures (3.35 ± 1.03 and 3.15± 0.74 L/min,
respectively), reaching a mean value of88.7 ± 9.0% compared to
basal. The small decrease inMCR could be almost completely ascribed to
hemodynamic factors;indeed, basal cardiac output (5.76 ± 1.70
L/min) wasfound, on the average, to be slightly decreased during
atrialand ventricular pacing (5.28 ± 1.46 and 5.16 ±1.33
L/min, respectively), and so whole body extraction of thehormone,
measured before pacing (50.0 ± 12%), remainsstable throughout
the study period (50.4 ± 10.6% and49.6 ± 10% during
atrial and ventricular pacing, respectively).Our findings demonstrate
that degradative mechanisms involvedin ANP clearance are not saturable
at least for acute elevationsof ANP plasma levels up to 3–5 times the
basal level.
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