THE KALLIKREIN-KININ SYSTEM, BUT NOT VASCULAR ENDOTHELIAL GROWTH-FACTOR, PLAYS A ROLE IN THE INCREASED VASCULAR-PERMEABILITY ASSOCIATED WITH OVARIAN HYPERSTIMULATION SYNDROME

Ovarian hyperstimulation syndrome (OHSS) is a severe complication aris ing from controlled stimulation treatment. Vascular endothelial growth factor (VEGF) has recently emerged as an important factor which may b e responsible for the hyperpermeability seen in OHSS. The purpose of t he present study was to investigate and compare the mechanisms by whic h ascites in patients with OHSS and ovarian carcinoma induce increases in vascular permeability in an in vitro assay and an in vivo animal e xperiment. We found 8-fold lower VEGF levels in ascites from patients with OHSS than in those from patients with ovarian carcinoma. Although VEGF is produced by the ovaries, it is not necessarily the factor res ponsible for hyperpermeability. We also demonstrated that the vascular hyperpermeability produced by OHSS ascites was not abolished by speci fic neutralizing anti-VEGF antibodies, and that not all of the VEGF fo und in the ascites fluid is biologically active. Moreover, our results strongly suggest that the vascular permeability produced by OHSS asci tes may depend on activation of the kallikrein-kinin system. Possible evidence for this phenomenon was obtained by demonstrating that the hy perpermeability caused by the ascites could be blocked by Trasylol (kn own to inhibit bradykinin synthesis) and potentiated by captopril (a k ininase II inhibitor). Taken together, the results suggest that, altho ugh VEGF is found in ascites fluid from patients with OHSS, it is unli kely that the cause of OHSS involves VEGF production by the ovaries. T he kallikrein-kinin system may be more important in the hyperpermeabil ity seen in OHSS.