Maternal High-Sucrose Diet Accelerates Vascular Stiffness in Aged Offspring via Suppressing Cav 1.2 and Contractile Phenotype of Vascular Smooth Muscle Cells.

Abstract

The fetal programming in response to over-nutrition during pregnancy is involved in pathogenesis of cardiovascular diseases later in life. The authors' previous work reported that prenatal high-sucrose (HS) diet impaired functions of large-conductance Ca2+ -activated K+ channels (BK) in mesenteric arteries in the adolescent offspring rats. This study determines whether prenatal HS has a long-term impact on resistance vasculature in the aged offspring rats. Pregnant rats are fed with a high-sucrose diet until delivery. Aged offspring from prenatal HS exhibit elevated fasting insulin level, insulin resistance index, and diastolic pressure. Both pressure-induced myogenic responses and phenylephrine-stimulated contraction of mesenteric arteries in HS are weakened. Electrophysiological tests and western blot indicate that BK and L-type calcium channels (Cav 1.2) are impaired in HS group. On the other hand, expression of matrix metalloproteinase 2 of mesenteric arteries is reduced in HS group while expression of tissue inhibitors of metalloproteinase is increased, indicating that extra cellular matrix (ECM) is remodeled. Furthermore, expression of α-smooth muscle actin is decreased, and insulin/insulin receptor/phosphoinositide3-kinase (PI3K) signaling pathway is downregulated. The results suggest that prenatal HS induced stiffness of mesenteric arteries in aged offspring by inhibiting Cav 1.2 function and PI3K-associated contractile phenotype of VSMCs.