Chronic fetal exposure to caffeine altered resistance vessel functions via RyRs-BKCa down-regulation in rat offspring.
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.
Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
Na
N
Li
Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
Yongmei
Y
Li
Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
Qinqin
Q
Gao
Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
Dawei
D
Li
Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
Jiaqi
J
Tang
Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
Miao
M
Sun
Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
Pengjie
P
Zhang
Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
Bailin
B
Liu
Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
Caiping
C
Mao
1] Institute for Fetology, First Hospital of Soochow University, Suzhou, China [2] Center for Perinatal Biology, Loma Linda University, California, USA.
Zhice
Z
Xu
D000818:Animals; D001794:Blood Pressure; D001835:Body Weight / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D019837:Ryanodine Receptor Calcium Release Channel; D013629:Tamoxifen; D010656:Phenylephrine; D002110:Caffeine; C064719:iberiotoxin; D002118:Calcium