Exaggerated prostaglandin and thromboxane synthesis in the rabbit with renal vein constriction.

Isolated perfused kidneys removed from a rabbit 24-48 hours after renal vein constriction exhibited a markedly enhanced release of renal prostaglandins (PG's) induced by vasoactive peptides. Stimulation of the perfused renal vein-constricted kidney with 300 ng of bradykinin (BK) caused the release of 5980 1409 ng of PGE 2 compared to a release of 290 45 ng from the contralateral control kidney. Infusion of indomethacin abolished the PGE 2 formation (confirmed by radiochromatography) in both the renal vein-constricted and contralateral kidneys. Bradykinin and angiotensin II stimulation of the renal vein-constricted kidney (but not the contralateral kidney) also revealed the presence in the renal venous effluent of a rabbit aorta-contracting substance (RCS). Identification of the RCS as thromboxane A 2 (TxA 2 ) was confirmed by determining the biological half life (38 6 sec) in comparison with standard TxA 2 (30 3 sec) and PG endoperoxide (135 13 sec). Incubation with [ l4 C]arachidonate of the renal vein-constricted cortical or medullary microsomes resulted in the formation of [ 14 C]thromboxane B 2 . The renal thromboxane synthetase was inhibited by preincubation with imidazole. This study demonstrates exaggerated prostaglandin and thromboxane production by the kidney with renal vein constriction. These in vitro experiments suggest that relative changes in cortical synthesis of vasodilating PGE 2 and vasoconstricting TxA 2 may function to modulate renal vascular resistance in states of increased renal venous pressure. Circ Res 47: [231][232][233][234][235][236][237] 1980 THE KIDNEY is a major site for synthesis of the vasodepressor prostaglandins (PG's). Increasing evidence implicates these agents in the regulation of the renal circulation Augmented vasodepressor PG release in response to ischemia (McGiff et al., 1970a), vasoactive hormones Prostaglandin E2 (PGE 2 ) is the major renal PG and exhibits these vasodepressor properties However, the increase in vascular resistance associated with high renal perfusion has not been associated with decreased PGE 2 synthesis and, instead, may be related to synthesis of another product of arachidonate metabolism and a potent vasoconstrictor, thromboxane A 2 (TxA 2 ). Exaggerated synthesis of TxA 2 has been identified previously only in the isolated hydronephrotic kidney (HNK) of the rabbit (Morrison et al., 1978a). Biosynthesis of both TxA 2 and PGE 2 has been identified in the renal cortex, the major site of resistance vessels (Morrison et al., 1978b; Thus, an interplay of these vasodepressor and vasoconstric-