The kallikrein-kinin system, but not vascular endothelial growth factor, plays a role in the increased vascular permeability associated with ovarian hyperstimulation syndrome

• Published in: Journal of molecular endocrinology Vol. 20; no. 3; pp. 363 - 374
• Main Authors: Kobayashi, H, Okada, Y, Asahina, T, Gotoh, J, Terao, T
• Format: Journal Article
• Language: English
• Published: England BioScientifica 01.06.1998
• Subjects: Adult; Aged; Amino Acid Sequence; Antibodies; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Ascites; Blotting, Western; Capillary Permeability; Chorionic Gonadotropin; Endothelial Growth Factors - analysis; Endothelial Growth Factors - biosynthesis; Endothelial Growth Factors - physiology; Estradiol - blood; Female; Fertilization in Vitro; Humans; Kallikreins - metabolism; Kinins - metabolism; Lymphokines - analysis; Lymphokines - biosynthesis; Lymphokines - physiology; Middle Aged; Molecular Sequence Data; Neoplasm Staging; Ovarian Hyperstimulation Syndrome - etiology; Ovarian Hyperstimulation Syndrome - physiopathology; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Ovarian Neoplasms - physiopathology; Ovulation Induction - adverse effects; Ovulation Induction - methods; Peptide Fragments - chemistry; Peptide Fragments - immunology; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
• ISSN: 0952-5041; 1479-6813
• DOI: 10.1677/jme.0.0200363

Ovarian hyperstimulation syndrome (OHSS) is a severe complication arising from controlled stimulation treatment. Vascular endothelial growth factor (VEGF) has recently emerged as an important factor which may be responsible for the hyperpermeability seen in OHSS. The purpose of the present study was to investigate and compare the mechanisms by which ascites in patients with OHSS and ovarian carcinoma induce increases in vascular permeability in an in vitro assay and an in vivo animal experiment. 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 responsible for hyperpermeability. We also demonstrated that the vascular hyperpermeability produced by OHSS ascites was not abolished by specific neutralizing anti-VEGF antibodies, and that not all of the VEGF found in the ascites fluid is biologically active. Moreover, our results strongly suggest that the vascular permeability produced by OHSS ascites may depend on activation of the kallikrein-kinin system. Possible evidence for this phenomenon was obtained by demonstrating that the hyperpermeability caused by the ascites could be blocked by Trasylol (known to inhibit bradykinin synthesis) and potentiated by captopril (a kininase II inhibitor). Taken together, the results suggest that, although VEGF is found in ascites fluid from patients with OHSS, it is unlikely that the cause of OHSS involves VEGF production by the ovaries. The kallikrein-kinin system may be more important in the hyperpermeability seen in OHSS.