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Published on: May 5, 2018
Chronic fetal exposure to caffeine altered resistance vessel functions via RyRs-BKCa down-regulation in rat offspring
Na Li1, Yongmei Li1, Qinqin Gao1
1Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
Insights
Prenatal caffeine exposure alters offspring vascular function by reducing large conductance calcium-activated potassium (BKCa) channels and ryanodine receptor (RyR) activity, potentially increasing hypertension risk.
Area of Science:
- Cardiovascular Physiology
- Developmental Origins of Health and Disease
- Pharmacology
Background:
- Caffeine is known to affect vascular and cardiac contractility.
- Embryonic exposure to caffeine has been shown to alter cardiac functions in offspring.
- The long-term effects of prenatal caffeine exposure on vascular function require further investigation.
Purpose of the Study:
- To determine the chronic influence of prenatal caffeine exposure on vascular functions in adult offspring.
- To investigate the impact of prenatal caffeine on ion channel activity in smooth muscle cells of mesenteric arteries.
Main Methods:
- Pregnant Sprague-Dawley rats were exposed to a high dose of caffeine.
- Vascular functions of mesenteric arteries (MA) and ion channel activities in smooth muscle cells of 5-month-old offspring were assessed.
- Techniques included measurement of pressor responses, vasoconstriction, membrane depolarization, whole-cell currents, single channel recordings, and [Ca2+]i fluorescence.
Main Results:
- Prenatal caffeine exposure led to increased pressor responses and phenylephrine-induced vasoconstrictions.
- Large conductance Ca2+-activated K+ (BKCa) channel activity, including whole-cell currents and spontaneous transient outward currents (STOCs), was decreased.
- Reduced voltage/Ca2+ sensitivity of BKCa channels and down-regulation of ryanodine receptors (RyRs) were observed, leading to diminished BKCa activation and enhanced vascular tone.
Conclusions:
- Prenatal caffeine exposure alters the biophysical properties and function of BKCa channels in the mesenteric arteries of offspring.
- Down-regulation of RyRs-BKCa signaling contributes to altered STOCs activity and enhanced vascular tone.
- These findings suggest a potential mechanism linking prenatal caffeine exposure to an increased risk of hypertension.
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.
