Vasodilator-stimulated phosphoprotein expression and its cytokine-mediated regulation in vasculogenesis during human placental development.

Vasculogenesis and the subsequent step, angiogenesis, are the most important stages for the continuity of placental development. Vasodilator-stimulated phosphoprotein (VASP) has a widespread role in the control of cell motility and participates in filamentous actin formation. We hypothesized that VASP participates in vasculogenesis and angiogenesis, by regulating endothelial cell migration. We therefore studied VASP expression in vasculogenic sites in placenta throughout pregnancy and the effect of vascular endothelial growth factor (VEGF) and interleukin (IL)-8 on the regulation of VASP expression in placental explant cultures. We found that VASP is expressed in a spatially and temporally regulated manner by various cells of the villi. In the villous stroma, the most intense immunoreactivity was observed in vasculogenic areas and in endothelial cells. In the second and third trimesters, endothelial cells demonstrated weaker immunoreactivity for VASP compared to samples from first trimester. Ultrastructural analysis of corresponding sites for VASP showed that this protein was increased in pre-endothelial cells. Areas of the strongest VEGF and IL-8 expression by villous trophoblasts corresponded to the areas of strongest VASP expression by endothelial cells, and VEGF and IL-8 showed a stimulatory effect on VASP expression in placental explants (P < 0.05). These results suggest that VASP may participate in vasculogenesis and endothelial sprouting during placental vasculogenesis. In addition, one of the effects of VEGF and IL-8 in angiogenesis may be to induce VASP expression in a paracrine manner.

Effect of exercise on blood pressure in rats with chronic NOS inhibition.

Regular training lowers blood pressure in hypertensive humans and other animals. We investigated the response to 4 weeks of treadmill exercise training in hypertensive male Wistar rats receiving the nitric oxide synthase inhibitor N(omega)-nitro- L-arginine methyl ester ( L-NAME). The rats were on either a short- (4 weeks) or long-term (10 weeks) L-NAME treatment protocol and were subjected to running exercise that started concomitantly in the short-term group and in the 6th week in the long-term group. Four weeks of exercise training induced a fall in mean arterial pressure in both the short- [mean (SEM) 137.6 (4.0) mmHg] and long-term hypertensive groups [161.4 (2.3) mmHg] compared to their sedentary hypertensive controls [160.4 (3.3) mmHg and 176.8 (8.9) mmHg, respectively]. Exercise also increased muscle nitric oxide synthase activity in both of the trained hypertensive groups. Muscle nitrite levels were higher in the exercising short-term hypertensive group compared to both the sedentary control and the sedentary hypertensive groups, and were not different between the sedentary and exercising long-term hypertensive groups. Increased wall thickness of the aortic and mesenteric vessels was observed in the hypertensive groups, but was prevented in the exercising long-term hypertensive group. In rat, exercise reduces the elevated blood pressure in L-NAME-induced hypertension via increasing nitric oxide synthase activity. Changes in vessel structure with exercise training may also be involved in the blood-pressure-lowering effects.