Pharmacokinetics and renal metabolism of atrial natriuretic factor during rat pregnancy. Omer, Saeed, Daya R. Varma, Peter Cernacek, and Shree Mulay. Departments of Physiology and Medicine and Cardiology Division, Royal Victoria Hospital, Montreal, Canada H3A 1A1; and Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada H3G 1Y6
APStracts 3:0049F, 1996.
The present studies were done to determine if the attenuation of the natriuretic/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/min) 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/[mu]g protein) 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 (NEP) 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.

Received 28 September 1995; accepted in final form 27 February
1996.
APS Manuscript Number F325-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 20 March 96