Study On The Effects Of BK_Ca Channels In Adult Offspring Rats By Prenatal High-sucrose Diets And The Underlying Mechanisms

Objectives:To investigate the effects of maternal high sucrose diet on the BK _Ca channels in offpring rat mesenteric artery and its related mechanisms.Methods:O ne female rat mated with two male rats.The day vaginal plugs detected was regarded as the first day of gestation.Following delivery,all pregnant rats were provided tap water and standard rat food.Pregnant rats were randomly divided into control group and high-sucrose group,10 rats in each group.The rats in high-sucrose group were provided with 20%sucrose solution diets throughout the gestation.Fetal blood samples were collected by decapitation.Blood samples of maternal rats and offspring were obtained from the abdominal aorta.All samples were collected into iced plastic tubes containing heparin.Blood glucose was determined by glucoseoxidase methods.Weight of fetus and offspring was measured at the same time.Vessel tone and electro-physiology were measured with DMT and patch clamp technique in offspring.Moreover,the expression levels of related genes and proteins were detected by RT-PCR or Western blot.Results:?1?Compared to the control,the weight of fetuses and b lood glucose was higher in the HS group.?2?Following intravenous PE,MAP was significantly higher in the HS offspring than that of the control while the baselines of mean arterial pressure?MAP?in two groups were no significant difference.Vasoconstriction to PE was significantly increased in CON but nothing was changed afrer adding iberiotoxin?IBTX?in the mesenteric artery of HS.The whole-cell current density and IBTX-sensitive current density as well as NPo of single BK _Ca channels in mesenteric vascular smooth muscle cells were decreased in the HS group.Expressions of BK_Ca?-,?1-subunits were significantly reduced in the mesenteries from the HS group.?3?Compared to the control,prenatal HS increased O₂^-production?DHE?and altered the expression of NOX4 and SOD1?Western blot?.?4?Between the presence and absence of apocynin,PE-induced maximum vasoconstriction showed no significant difference in CON,while that was decreased in HS group.When comparing effects of IBTX on vasoconstriction in presence or absence of apocynin,pre-incubation with apocynin enhanced extent of IBTX-raised vasoconstriction in HS group.Compared with slight influence of apocynin on BK_Ca currents of CON VSMCs,BK_Ca currents of HS were elevated by apocynin.To single current,open time of HS was restored by apocynin while close time was still longer t han that of CON.Thus,although NPo of HS single current in presence of apocynin was increased,it was lower than that of CON.?5?The expression of phospho-AKT,not total AKT,was markedly reduced in HS group,resulting in a decrease of phospho-AKT/AKT ratio of HS vessels compared to that in CON.The mRNA level of Fbxo32 was increased in HS group.Conclusions:The oxidative stress of the mesenteric vessels in the HS offspring was enhanced with up-regulated NOX4 and down-regulated SOD1,thus affecting the blood vessel tension,current density and molecular expression by alteration of AKT/FBXO32signaling pathway,resulting in increased risk of hypertension in offspring.