Maternal high-sucrose diets altered vascular large-conductance Ca2+-activated K+ channels via reactive oxygen species in offspring rats†

Abstract

Overnutrition during pregnancy could increase risks of cardiovascular diseases in late life. This study investigated whether and how reactive oxygen species (ROS) may influence functions of large-conductance Ca2+-activated K+ channels (BKCa) in the offspring exposed to prenatal high sucrose (HS). We found that prenatal HS diets significantly increased phenylephrine (PE)-induced vessel contractions in mesenteric arteries of the adult offspring. Pretreatment with iberiotoxin (BKCa blocker, IBTX) significantly increased PE-mediated vascular contractions in the control, not in the HS group. Electrophysiological studies demonstrated that BKCa current density and single-channel current were reduced in the vascular smooth muscle cells (VSMCs) of the HS offspring. The expression of BKCa alpha, beta1 subunits in mesenteric arteries was decreased in the HS offspring, indicating that both activity and number of BKCa channels in HS offspring were reduced. Superoxide production and NADPH oxidase (NOX)4 of the HS offspring were elevated. Following inhibiting NOX by apocynin, vasoconstriction in the HS offspring was weakened and the reduced currents in the VSMCs were improved with altered protein kinase B (AKT) pathway. The results suggested that NOX4-derived ROS might inhibit the offspring vascular BKCa channel activity via AKT pathway.

Maternal High‐Sucrose Diet Accelerates Vascular Stiffness in Aged Offspring via Suppressing Cav1.2 and Contractile Phenotype of Vascular Smooth Muscle Cells

“…Our previous study reported that no significant difference was observed in body weight between the CON and HS offspring at young adult stage . However, the average body weight of aged offspring was higher in the HS group than that in CON ( Table ).…”

“…However, the average body weight of aged offspring was higher in the HS group than that in CON ( Table ). Though the blood glucose levels in fetal and adult HS group were higher when compared with CON, there was no significant difference in the aged offspring between CON and HS groups (Table ). Whereas, FINS and HOMA‐IR index of aged HS group were higher than that of the CON (Table ).…”

“…We found that maternal over‐consumption of sucrose could enhance the PE‐induced tension by impairing BK functions in mesenteric arteries in the young adult offspring . To examine whether this change extend from youth to old age, BK activities in PE‐induced tension in aged rats were assessed.…”

“…Total RNA of mesenteric arteries from aged offspring was extracted using Trizol reagent (Takara, China) following manufacturer's instructions . The concentration and purity of extracted RNA were confirmed by spectrophotometer (Thermo, USA).…”

“…Our previous study demonstrated that over consumption of sucrose during pregnancy could elevate blood glucose level and enhance vascular tension in young adult offspring rats. The possible mechanism was linked to the inhibited functions of large‐conductance Ca 2+ ‐activated K + channels (BK) . However, there is still a lack of underlying mechanisms to interpret the association of the metabolic syndrome with cardiovascular diseases, especially in the aged offspring exposed to prenatal high‐sucrose (HS) diet.…”