VASCULAR EFFECTS ALTER EARLY-GESTATION FETAL RENAL RESPONSES TO VASOPRESSIN

Distinct receptors mediate the vascular (V-1) and renal (V-2) effects of arginine vasopressin (AVP). Although ovine fetal AW-induced antidiuresis can be demonstrated in early gestation (< 120 days; term 150 days), the early-gestation fetal renal responses to AVP are variable, including increases in urine flow and glomerular filtration rate (GFR). AVP V-1 receptor predominance and/or V-2 receptor system immaturity may contribute to variable early-gestation renal responses to AVP. To differentiate these possibilities, we assessed early-gestation fetal V-2 receptor function in the presence and absence of V-1 receptor-mediated effects by comparing the responses to AVP (a combined V-1-V-2 receptor agonist; n = 10; 112 +/- 2 days) with the selective V-2-receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP) (n = 5; 111 +/- 2 days). AVP infusion increased fetal mean arterial pressure (MAP; 36 +/- 1 to 44 +/- 2 mmHg) and decreased heart rate (197 +/- 2 to 171 +/- 3 beats/min); DDAVP infusion had no effect on MAP or heart rate. Free water clearance decreased in response to AVP (0.13 +/- 0.02 to 0.02 +/- 0.01 ml.min(-1).kg(-1)) and DDAVP (0.21 +/- 0.04 to 0.04 +/- 0.02 ml.min(-1).kg(-1)), and urine osmolality increased in response to both analogues (AVP: 145 +/- 4 to 283 +/- 15 mosmol/kgH(2)O; DDAVP: 146 +/- 5 to 244 +/- 32 mosmol/kgH(2)O). AVP infusion had no effect on urine flow (0.26 +/- 0.03 to 0.26 +/- 0.03 ml.min(-1).kg(-1)) and increased GFR (1.3 +/- 0.1 to 2.1 +/- 0.2 ml.min(-1).kg(-1)) and fractional sodium excretion (4.6 +/- 0.7 to 8.2 +/- 1.2%). In contrast, DDAVP infusion decreased urine flow (0.40 +/- 0.08 to 0.19 +/- 0.05 ml.min(-1).kg(-1)) without affecting GFR (2.0 +/- 0.3 to 1.6 +/- 0.3 ml.min(-1).kg(-1)) or fractional sodium excretion (5.8 +/- 1.0 to 5.9 +/- 1.0%). We conclude that AVP V-2 receptor activation appropriately increases early-gestation fetal renal water reabsorption. Thus, because of limitations in GFR autoregulation and sodium reabsorption, the limited antidiuretic response to AW in early-gestation fetuses reflects a glomerulotubular imbalance secondary to AVP V-1 receptor-induced changes in systemic blood pressure,