Intake of high sucrose during pregnancy altered large-conductance Ca2+-activated K+ channels and vessel tone in offspring’s mesenteric arteries

Abstract

Antenatal malnutrition could be linked to hypertension and vascular diseases in fetal origins. This study determined the influence of maternal intake of high sucrose (HS) during pregnancy on vessel tone, intracellular Ca(2+) ([Ca(2+)](i)), K(+) channels, especially large-conductance Ca(2+)-activated K(+) channels (BK), in mesenteric arteries in the offspring rats exposed to prenatal HS. Vessel tension and [Ca(2+)](i) induced by angiotensin II were higher in the small mesenteric arteries of the HS offspring. In the vascular smooth muscle cells (VSMCs) from the HS offspring, electrophysiological studies showed depressed BK current density and depolarized membrane. Western blot showed altered expressions of BK α-subunits, AT1 and AT2 receptors in mesenteric arteries. The results suggest that decreased BK channel activity and depolarized membrane potential in the VSMCs partly contributed to the increased vessel tone and [Ca(2+)](i) in the HS offspring, adding new information for understanding mechanisms in vascular malfunctions in fetal origins, and novel insights for early prevention and treatments against such vascular diseases.

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

“…Contrarily, the reduction in BKCa channel activity due to channel dysfunction in vascular smooth cells can blunt the negative regulation of vessel tone [33,37,38]. Recent studies have shown that BKCa channels have a pathophysiological role in the development of adverse cardiovascular outcomes following exposure to prenatal insults [12,16]. Our vasoconstriction and electrophysiological data suggested that AII-induced vasoconstrictions in HS offspring’s MCA were partially attributed to the reduced BKCa channel activity, which could be explained in either of two ways: (1) as shown in whole-cell K + currents data, the baseline of whole-cell K + currents as well as the decreased K + currents by the BKCa channels inhibitor were reduced in HS group, indicating that BKCa currents in HS offspring’s MCA were less than that in the control.…”

“…Rings of MCA were carefully prepared, and mounted in a multimyograph system (Danish Myo Technology, Midtjylland, Denmark) for recording of isometric tension [3,12]. The vessel rings were given an initial tension and were equilibrated for 60 min.…”

“…Myocytes were isolated enzymatically from dissected MCA [2,12]. Briefly, MCA were first dissected gently and cut into small fragments (approximately 0.5 mm) in oxygenated ice-cold physiological solution (PSS) (mmol/l: NaCl, 120.9; NaHCO 3 , 25.0; KCl, 4.6; NaH 2 PO 4 , 1.2; MgCl 2 , 1.2; CaCl 2 ·2H 2 O, 2.8; and glucose, 5.0; pH 7.4), and then were placed for 35 min at 37°C in PSS solution containing 5 mg/ml papain, 2 mg/ml ABV, and 1 mg/ml dithiothreitol.…”

“…Feeding mother rats with a diet high in sugar could cause adverse outcomes such as cardiovascular diseases and metabolic syndrome in the offspring [10,11]. Our previous study demonstrated that high sucrose (HS) diets during pregnancy not only altered microvessel tone via depressed BKCa channels in offspring’s mesenteric arteries [12], but also led to impaired learning and memory in the male offspring [13]. Since middle cerebral artery (MCA) is a critical blood vessel in supplying blood and oxygen to the brain, MCA dysfunction could be considered as major contributor to multiple brain problems, such as vascular dementia and cognitive dysfunction [14,15].…”

Roles of ion channels in regulation of acetylcholine-mediated vasoconstrictions in umbilical cords of rabbit/rats

“…At gestational day (GD) 21, rats were anesthetized with a mixture of ketamine (75 mg/kg) and xylazine (10 mg/kg; Hengrui Medicine, Jiangsu, China) intraperitoneally [18] and at GD 26, rabbits were anesthetized intravenously with ketamine (30 mg/kg) [19] through an ear vein followed with uterine-incision delivery. Umbilical cords were collected and kept in Ca 2+ -free physiological salt solution.…”