METABOLIC-CLEARANCE OF VASOPRESSIN AND AN ANALOG RESISTANT TO VASOPRESSINASE IN HUMAN-PREGNANCY

The metabolic clearance rate (MCR) of arginine vasopressin (AVP) increases fourfold during human pregnancy. To explore whether circulating vasopressinase may play a role in this change, six women underwent a three-tier infusion clearance study, twice, in random order, to determine the MCRs of either AVP or 1-deamino-8-D-AVP (dDAVP, an analogue resistant to degradation by vasopressinase). Volunteers were tested in late pregnancy (LP), 24-48 h postdelivery (PD), and 5-6 (PP1) and 10-12 (PP2) wk postpartum, thus examining MCRs when vasopressinase levels were high, before and after removal of the placenta (LP and PD), and when plasma enzyme activity was becoming (PP1) and became (PP2) undetectable. Manipulation of infusate permitted comparison of MCRs at three plasma levels whose range was similar at each test period. P(AVP) and P(dDAVP) (2.2 and 10 pg/ml, respectively, during the initial infusion) increased to 8 and 31 pg/ml, stepwise increments that had no influence on respective MCRs (AVP: 3.4, 2.2, 0.77, and 0.67 I/min during LP, PD, PP1, and PP2 compared with 0.18,0.21, 0.17, and 0.15 1/min for dDAVP). Comparison of similar and submaximal urinary osmolality revealed P(dDAVP) Values three-to fourfold greater than P(AVP). Von Willebrand factor (VWF) and factor VIIIc levels increased almost fourfold in response to dDAVP during pregnancy, but only doubled in the nonpregnant state; these differences did not reach significance. We conclude that although AVP disposal rates increase fourfold in pregnancy, those of dDAVP change little, suggesting a role of vasopressinase in the increased MCR of AVP in gestation (as well as in the genesis of certain polyuric disorders of pregnancy). The antidiuretic potency of dDAVP is less than that of AVP, its greater efficacy due to its markedly prolonged clearance from plasma. Finally, dDAVP appears to provoke greater increments in VWF and factor VIIIc during gestation.