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  • Chronic fetal exposure to caffeine altered resistance vessel functions via RyRs-BKCa down-regulation in rat offspring.

Chronic fetal exposure to caffeine altered resistance vessel functions via RyRs-BKCa down-regulation in rat offspring.

Scientific reports (2015-08-19)
Na Li, Yongmei Li, Qinqin Gao, Dawei Li, Jiaqi Tang, Miao Sun, Pengjie Zhang, Bailin Liu, Caiping Mao, Zhice Xu
ABSTRACT

Caffeine modifies vascular/cardiac contractility. Embryonic exposure to caffeine altered cardiac functions in offspring. This study determined chronic influence of prenatal caffeine on vessel functions in offspring. Pregnant Sprague-Dawley rats (5-month-old) were exposed to high dose of caffeine, their offspring (5-month-old) were tested for vascular functions in mesenteric arteries (MA) and ion channel activities in smooth muscle cells. Prenatal exposure to caffeine increased pressor responses and vasoconstrictions to phenylephrine, accompanied by enhanced membrane depolarization. Large conductance Ca2(+)-activated K(+) (BKCa) channels in buffering phenylephrine-induced vasoconstrictions was decreased, whole cell BKCa currents and spontaneous transient outward currents (STOCs) were decreased. Single channel recordings revealed reduced voltage/Ca(2+) sensitivity of BKCa channels. BKCa α-subunit expression was unchanged, BKCa β1-subunit and sensitivity of BKCa to tamoxifen were reduced in the caffeine offspring as altered biophysical properties of BKCa in the MA. Simultaneous [Ca(2+)]i fluorescence and vasoconstriction testing showed reduced Ca(2+), leading to diminished BKCa activation via ryanodine receptor Ca(2+) release channels (RyRs), causing enhanced vascular tone. Reduced RyR1 was greater than that of RyR3. The results suggest that the altered STOCs activity in the caffeine offspring could attribute to down-regulation of RyRs-BKCa, providing new information for further understanding increased risks of hypertension in developmental origins.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Fura 2-AM, ≥95% (HPLC)
Sigma-Aldrich
Fura 2-AM, BioReagent, suitable for fluorescence, ≥95.0% (HPLC)