Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, PC182
Vasorelaxant effect of genistein and Vascular Endothelial Growth Factor (VEGF) in rat?
A. R. Fernandez1, S. Z. Omar2, R. Husain1
1. Dept. of Physiology, University of Malaya, Kuala Lumpur, Malaysia. 2. Dept. of Obstetrics & Gynaecology, University Malaya Medical Center, Kuala Lumpur, Malaysia.
Vascular endothelial growth factor (VEGF) is an endogenous proangiogenic factor and a vasodilator which help maintain endothelial health. However in preeclampsia, there is excessive circulating antiangiogenic factor soluble fms-like tyrosine kinase 1 (sFlt1) which tends to bind to VEGF rendering it ineffective thus leading to generalised vasospasm (1). Genistein is a soy-derived isoflavone and a powerful vasodilator (2). We postulate that genistein may be able to overcome the vasospasm in preeclampsia. Using isolated rat’s aorta, we investigated the vasodilatory effect of genistein in the presence of VEGF and vice versa. Thoracic aorta of male Sprague-Dawley rats were used in the experiments. Aortic rings (3-4mm) was suspended in 10ml tissue bath containing Kreb’s solution. Changes in isometric tension were recorded using a force-displacement transducer connected to a Power Lab system(AD Instruments, Australia). Relaxation response studies to genistein (1 × 10-5 - 30 × 10-5M) and VEGF(2.6 × 10-11 - 7.9 × 10-9M) were done following preconstriction with phenyInephrine 10-7M (n=6). Aortic rings were incubated with genistein (5 × 10-5M) for 10 minutes and subjected to cumulatively added increasing doses of VEGF after preconstriction with phenylephrine(n=7). In another series of experiment, tissue were incubated with VEGF (7.9 × 10-10M) for 10 minutes, preconstricted with phenylephrine and then subjected to increasing doses of genistein (n=6). All experiments were conducted on endothelium intact rings. Data are presented as mean± SEM. Comparisons of the percentage relaxation with and without genistein were tested by two-way repeated measures ANOVA, with p < 0.05 considered as significant. Both genistein and VEGF induced vasodilatation of the aortic rings (Emax: 117.7 ± 7.7% and 52.5 ± 7.3% respectively). Incubation of aortic ring with genistein at 5 × 10 -5M, enhanced the vasodilatory effect of VEGF [ Emax: 86.2 ± 6.3%; F(1,5)=7.54, p<0.05] . The presence of VEGF, caused small and statistically insignificant shift of the genistein dose-response curve to the left. The results trigger the suggestion that genistein may help overcome the vasospasm in preeclampsia. It may be a promising therapeutic approach to preeclampsia.
Where applicable, experiments conform with Society ethical requirements