This study determines the influence of a prenatal high-sucrose (HS) diet on angiotensin II (Ang II)-mediated pressor response and determine the underlying mechanism. Pregnant rats were provided with a 20% sucrose solution diet throughout gestation. Blood pressure and vascular response to Ang II were measured in 5-month-old adult offspring. Currents of L-type Ca(2+) channels (Cav1.2) were measured in smooth muscle cells of small mesenteric arteries from the offspring. Ang II-mediated pressor response was higher in the offspring exposed to prenatal high sugar compared with the control. In mesenteric arteries from the HS offspring, AT1 receptors (AT1R), not AT2 receptors, mediated the increased vasoconstriction; protein kinase C (PKC) antagonist GF109203X suppressed the Ang II-increased vasoconstriction; PKC agonist phorbol 12,13-dibutyrate produced a greater contractile response that was reversed by the Cav1.2 antagonist nifedipine. The expression of PKCα was increased, whereas PKCδ was unchanged; KCl-induced vasoconstriction was stronger and was suppressed by nifedipine; nifedipine also reduced the enhanced vasoconstriction by Ang II. In addition, the Cav1.2 of smooth muscle cells in mesenteric arteries from the HS offspring showed larger current density, although its expression was unchanged. The data suggest that a HS diet during pregnancy alters Ang II-mediated pressor response and microvessel tone acting through the PKC/Cav1.2 pathway in the offspring that may in part be because of alterations in AT1Rs, PKCα and Cav1.2.