Regulation of cerebral arterial BKCa channels by angiotensin II signaling in adult offspring exposed to prenatal high sucrose diets.

Xiuxia Gu,Ruixiu Shi,Lin Jiang,Le Bo,Yuxian Yang,Xiaorong Fan,Zhice Xu,Na Li,Qinqin Gao,Jue Wu,Axin He,Xueqin Feng

doi:10.1042/bsr20160624

Abstract

Prenatal insults have been shown to affect vascular functions, leading to increased risks of cardiovascular diseases in offspring. The present study determined whether high sucrose (HS) intake in pregnancy affected central vascular functions in middle cerebral artery (MCA) of offspring. Sprague-Dawley rats were fed a standard food and tap water with normal or high (20%) sucrose content during pregnancy. Offspring were maintained with normal diets and tap water. Central vascular functions and related ion channels were assessed in male offspring at 5 months old. Compared with the control, angiotensin II (AII)-induced vasoconstrictions were significantly higher in the MCA of the offspring exposed to prenatal HS. In the MCA, large conductance Ca2+-activated K+ channels (BKCa) currents were decreased with a reduction of opening frequency, sensitivity to intracellular Ca2+/membrane voltage, and BKβ1 expression. mRNA levels of AT1α and AT2, as well as AT1/AT2 ratio, were significantly increased in the MCA of offspring following exposure to prenatal HS diets. The data suggested that prenatal HS diets could alter microvascular activities in the MCA, probably via changes of BKCa channels in the brain.

Highlights

The hypothesis of ‘fetal programming of adult diseases’ proposed by Barker postulated that impaired in utero growths are determinants of diseases in adult life [1]
Compared with that in the control, the maximal response to angiotensin II (AII) was significantly increased in middle cerebral artery (MCA) from the high sucrose (HS) offspring
The present study demonstrated that prenatal HS diets could affect fetal development in utero, and increase risks of cerebral dysfunction in the adult offspring via adverse vascular functions in the MCA

Summary

Introduction

The hypothesis of ‘fetal programming of adult diseases’ proposed by Barker postulated that impaired in utero growths are determinants of diseases in adult life [1]. It is well known that vascular smooth muscle cells (VSMCs) play a key role in the control of vascular tone. Changes in VSMCs membrane potential regulated by K+ channels have been proposed to be involved in modulating physiological and pathophysiological vessel tone [5,6,7]. Four distinct types of K+ channels have been identified in VSMCs: voltage-dependent K+ channels, Ca2+-activated K+ (KCa) channels (including the large (BKCa), intermediate (IKCa), and small (SKCa) conductance subfamily), inward rectifier K+ channels, and ATP-sensitive K+ channels [7]. Among above K+ channels, BKCa channels are key subgroups to regulate membrane electrical events in virtually all VSMCs. Activation of BKCa channels can lead to hyperpolarization of cell membrane and provide a negative feedback in the modulation of vascular tone [8,9]

Methods

Results

Conclusion