In vitro renal eicosanoid production during pregnancy in rabbits

The low renal resistance to blood flow in the presence of an activated endogenous renin-angiotensin system in gravid animals may in part be mediated by the action of eicosanoids produced in situ. To evaluate intrarenal eicosanoid production during gestation in rabbits, we quantitated immunoreactive PGE₂, 6-keto-PGF(1α) (a stable metabolite of PGI₂) and thromboxane B₂ (a stable metabolite of thromboxane A₂) in unextracted media after incubation of renal slices and isolated glomeruli. In cortical slices from nonpregnant and pregnant rabbits, PGE₂ production (μg·g^-1·30 min^-1) was 0.04 ± 0.005 and 0.08 ± 0.01 (P < 0.01) and 6 keto-PGF(1α) was 0.03 ± 0.01 and 0.06 ± 0.001 (P < 0.05), respectively. In papillary slices, PGE₂ production was 14 ± 2 and 21 ± 2 (P < 0.05) and 6 keto-PGF(1α) was 4 ± 1 and 5 ± 1 (P > 0.05) for nonpregnant and pregnant rabbits, respectively. Thromboxane B₂ production was unchanged during pregnancy in both cortex and papilla. Acute captopril administration to nonpregnant and to pregnant rabbits in vivo failed to alter in vitro renal slice eicosanoid production. Isolated glomeruli from nonpregnant and pregnant rabbits synthesized PGE₂ at similar rates. Exogenous arachidonic acid increased PGE₂ production (P < 0.05), but angiotensin II had no effect on eicosanoid production in vitro. These data suggest that the net synthesis of vasodilator eicosanoids is enhanced during gestation in rabbits. The preferential enhancement of PGE₂ and PGI₂, relative to thromboxane A₂, synthase activities is likely to be related to a chronic modification in cellular function induced by one or more hormones in vivo.