The underlying etiology of many chronic diseases such as hypertension and diabetes has been traced to the in utero environment. Our interest has focused on determining the mechanism of programmed hypertension. In our rodent model of 50% maternal food restriction (MFR) from day 10 of gestation to term the offspring develop hypertension as adults. We hypothesized that maternal undernutrition inhibits angiogenesis such that the neonate is endowed with fewer microvessels, increasing their susceptibility to develop hypertension as adults. We found significantly reduced number of mesenteric branching and renal medullary microvessels in the 1 day old MFR newborns. Endothelial cells from MFR offspring generated shorter neovessels in culture as compared with controls. The inhibition of angiogenesis was associated with a significant decrease in VEGF protein expression in mesenteric microvessels and aortas in 1 day old offspring. However, in adulthood there was a marked increase in VEGF expression in both vessel types. The expression of eNOS protein was also found to be increased in both renal and mesenteric microvessels and in aortas in the 1 day old MFR offspring. These results suggest that MFR results in inhibition of VEGF expression in microvascular and aortic endothelial cells early in life resulting in decreased angiogenesis and increased peripheral vascular resistance, both of which may contribute to offspring hypertension.