Maternal High-salt Diet Altered PKC/MLC20 Pathway And Increased ANG Ⅱ Receptor-mediated Vasoconstriction In Adult Male Rat Offspring

Objectives: This study aims at ascertaining the influence of maternal high-salt(HSD) on offspring’s angiotensin II(ANG II)-mediated vasoconstriction and the underlying mechanisms.Main methods and results: In comparison to a normal-salt diet(NSD), HSD used in pregnancy in rats changed the ultrastructures of the coronary artery(CA) in 5-month-old male offspring, and increased ANGII-mediated CA contractility. Measurement of [Ca2+]i in CA using fluorescent fura-2, a Ca2+ indicator, showed that ANG II-mediated increases in [Ca2+]i were the same between HSD and NSD groups, but the ratio of diameter change/[Ca2+]i-induced by ANG II were significantly higher in HSD groups. Angiotensin II receptor type 1(AT1R), not AT2 R, caused ANG II-mediated vasoconstriction. Protein kinase C(PKC) inhibitor GF109203 X attenuated the ANG II-mediated vasoconstriction, PKC agonist phorbol12,13-dibutyrateproduced a greater contraction. There was an increase in PKCβ mRNA and the corresponding protein abundance in the offspring, whereas other PKC subunits PKCα, PKCδ, and PKCε did not change. Moreover, 20-kDa myosin light chain phosphorylationlevels were increased in HSD group.Conclusion: Maternal HSD affected the developmental programming for the offspring CA, with increased ANG II-mediated vasoconstrictions. The AT1R-PKC-MLC20-P pathway was the possible mediated cellular mechanism.