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- W4241053973 abstract "61 Placental ischemia during late pregnancy triggers the release of tumor necrosis factor α (TNFα), which may contribute to the increased vascular resistance associated with pregnancy-induced hypertension (PIH). We have reported that elevation of plasma TNFα 2-fold increases blood pressure and renal vascular resistance in pregnant rats; however, the cellular mechanisms involved are unclear. In this study, we investigated whether TNFα infusion in pregnant rats (10 ng/kg/day for 7 days) is associated with increases in [Ca 2+ ] i and contractility of renal arterial smooth muscle. Pregnant (MAP = 96±3mmHg), TNFα-infused pregnant (123±3mmHg), virgin (108±5mmHg) and TNFα-infused virgin (110±3mmHg) Sprague-Dawley rats were used. Single smooth muscle cells were freshly isolated from the renal interlobular arteries and loaded with fura-2. In cells of pregnant rats incubated in Hank’s solution (1 mM Ca 2+ ), the resting length was 74±6 μm and [Ca 2+ ] i was 82±4 nM. In TNFα-infused pregnant rats, the resting cell length was shorter (54±3 μm) and [Ca 2+ ] i was higher (119±4 nM) than pregnant rats. In pregnant rats, angiotensin II (AII, 10 -7 M) caused a transient increase in [Ca 2+ ] i to 372±9 nM, a maintained increase to 149±8 nM and 21±2% cell contraction. The Ca 2+ channel agonist BAY K8644 (10 -6 M) caused an increase in [Ca 2+ ] i to 249±11 nM and 18±2% cell contraction. In TNFα-infused pregnant rats, the maintained AII- and BAY K8644-induced [Ca 2+ ] i (186±4 and 307±6 nM) and cell contraction (29±3% and 27±3%) were significantly > pregnant rats. AII and BAY K8644-induced contraction and [Ca 2+ ] i were not significantly different between untreated and TNFα-infused virgin rats. In Ca 2+ -free Hank’s, AII and caffeine (10 mM)-induced [Ca 2+ ] i transient and cell contraction were not significantly different in different groups of rats. Thus, TNFα-induced hypertension in pregnant rats is associated with increased [Ca 2+ ] i in renal arterial smooth muscle cells due to enhanced Ca 2+ entry from extracellular space. TNFα, via increasing smooth muscle contractility and [Ca 2+ ] i , may represent a possible mediator of the increased vascular resistance associated with PIH." @default.
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- W4241053973 date "2000-10-01" @default.
- W4241053973 modified "2023-10-16" @default.
- W4241053973 title "Tnfα-Induced Hypertension in Pregnant Rats Is Associated with Increased [Ca 2+ ] I Signaling in Renal Arterial Smooth Muscle" @default.
- W4241053973 doi "https://doi.org/10.1161/hyp.36.suppl_1.688-e" @default.
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