Renal effects of aprotinin after 24 hours of unilateral ureteral obstruction.
We have previously demonstrated that, after the release of 24-h unilateral ureteral obstruction (UUO), glomerular filtration rate (GFR), and renal blood flow (RBF) are reduced because of increased production of the potent vasoconstrictors thromboxane A2 (TxA2) and angiotensin II (ANG II). Captopril, which blocks ANG II production, increases GFR and RBF. Sequential administration of aprotinin, a kallikrein inhibitor, has an additive effect to further decrease renal vasoconstriction, even though kinins are generally thought to be vasodilators. Therefore, we assessed mechanisms by which aprotinin might improve renal function of previously obstructed anesthetized rats. When given alone to UUO rats, aprotinin improved renal hemodynamics. Since kinins stimulate TxA2 production by UUO kidneys perfused in vitro, our data suggest that aprotinin improved postobstructive function by decreasing kinin-stimulated TxA2 production, although this may not be its only effect. Aprotinin also improved postobstructive function, even if TxA2 formation was blocked with indomethacin. But when both ANG II and TxA2 formation were blocked by the simultaneous administration of captopril and indomethacin, aprotinin had no effect. This suggests that aprotinin may also affect ANG II formation. These pharmacological effects of aprotinin suggest that the kallikrein-kinin system may also contribute to postobstructive renal vasoconstriction by stimulating the production of both vasoconstrictor eicosanoids and ANG II.
D000804:Angiotensin II / Q000096:biosynthesis; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D013928:Thromboxane A2 / Q000096:biosynthesis; D014517:Ureteral Obstruction / Q000503:physiopathology*
D000804:Angiotensin II; D013928:Thromboxane A2; D007611:Aprotinin; D002216:Captopril