AJP - Renal Physiology, Vol 271, Issue 1 194-F197, Copyright © 1996 by American Physiological Society
Pharmacokinetics and renal metabolism of atrial natriuretic factor during rat pregnancy
S. Omer, D. R. Varma, P. Cernacek and S. Mulay
Department of Physiology, Royal Victoria Hospital, Montreal, Quebec, Canada.
The present studies were done to determine if the attenuation of the
natriuretic and diuretic effects of atrial natriuretic factor (ANF) during
rat pregnancy was caused by an increase in its metabolism. It was found
that the plasma half-life (min), plasma clearance (ml.kg-1.min-1), and
volume of distribution (ml/kg) of ANF were, respectively, 2.5 +/- 4, 115
+/- 19, and 371 +/- 44 in pentobarbital-anesthetized virgin rats (n = 6)
and not different from the corresponding values of 3.1 +/- 0.5, 124 +/- 26,
and 526 +/- 120 in 20-day gravid animals (n = 6). Rates of metabolism of
ANF (pmol.min-1.microgram protein-1) by renal cortical membranes from
virgin (n = 5) and gravid (n = 5) rats were, respectively, 45 +/- 0.6 and
45 +/- 0.5; likewise, cortical membrane neutral endopeptidase activities in
virgin and 20-day gravid rats (n = 7) did not differ. It is concluded that
the attenuation of the renal effects of ANF during pregnancy is not caused
by changes in its systemic or renal metabolism but might be due to a
decrease in guanylate cyclase-linked renal ANF receptors and/or
receptor-mediated effects.
