Vascular endothelial growth factor increases the ultrafiltration coefficient in isolated intact Wistar rat glomeruli

摘要: Vascular endothelial growth factor (VEGF) was originally described by its ability to increase macromolecular extravasation in the systemic circulation (Senger et al. 1983), hence initial term ‘vascular permeability factor’. Subsequent investigations have shown that VEGF increases microvessel both water (Bates & Curry, 1996) and albumin (Wu alters vessel diameter compliance (Bates, 1998). also plays a fundamental role cell maintenance angiogenesis (Ferrara, 2004). associated receptors are strongly expressed renal glomeruli, traditionally considered exhibit trans-basement membrane distribution. In situ hybridization reveals strong expression podocytes (Bailey 1999), cognate VEGFR-1 VEGFR-2 found on glomerular cells (Simon 1995). However, recent work suggests express (namely neuropilin-1, but not VEGFR-2), this coexpression of permits podocyte-mediated alterations podocyte behaviour, such as Ca2+ homeostasis (Foster 2003) nephrin phosphorylation 2005), representing functional autocrine effect. The components axis disturbed wide variety pathologies with altered (such proteinuria) (Schrijvers 2004), appears an important glomerulogenesis (Kitamoto 1997) repair from injury some animal models disease (e.g. Masuda 2001). induces fenestrations vitro (Esser 1998b), binds molecules which form basement membrane, heparan sulphate (Soker 1993), slit-diaphragm protein conditionally immortalized human 2005). anatomical arrangement axis, interact major filtration barrier vitro, led suggestion may contribute normal control 2004). In phase II study metastatic colon cancer (Kabbinavar 2003), significant excess patients treated monoclonal antibody therapy experienced proteinuria compared those group. Although occurrence replicated III (Hurwitz threshold value for 500 mg day−1 latter significantly exceeds pathological population (Johnson Feehally, 2003). Furthermore, abrogated hyperfiltration albuminuria diabetic rats, did affect these parameters rats (de Vriese Application noradrenaline-preconstricted vascular bed isolated perfused rat kidneys perfusion flow rate. no change rate or noted (Klanke therefore remains unclear 2004). Traditional, infrequently attempted, techniques examining at single-nephron level include direct capillary micropuncture (Brenner 1971) tubular stop-flow studies (Gertz 1966). profound haemodynamics induced Harper, likely complicate assessment ultrafiltration coefficient (LpA) using techniques. model developed Savin colleagues (Savin Terreros, 1981) characteristics isolation circulating haemodynamic influences. volumetric response glomerulus transglomerular oncotic gradient allows determination LpA. Values obtained technique been correspond well LpA values vivo (Maddox 1992). Using model, coworkers various mediators possess alter LpA, including angiotensin (Wiegmann 1990). We refined methods permit examination influence