Pharmacokinetics and renal metabolism of atrial natriuretic factor during rat pregnancy

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.