Medullary serotonin (5-hydroxytryptamine; 5-HT) neurons project to multiple autonomic nuclei in the CNS. Infant rats lacking 5-HT have low arterial blood pressure (ABP) in quiet sleep, but the role of 5-HT on ABP across vigilance states in adults has not been studied. We hypothesized that in adults, CNS 5-HT deficiency leads to hypotension mainly in wakefulness (QW) and non-rapid eye movement sleep (NREM), when 5-HT neurons are active. We tested male and female tryptophan hydroxylase 2 knockout rats (TPH2-/-), specifically deficient in CNS 5-HT, and wild-type (TPH2+/+) controls at 2-3, 5-8 and 12-13 months of age. Compared to TPH2+/+, mean arterial pressure of 5-8 and 12-13 month-old (middle-aged) male TPH2-/- rats was significantly elevated (~10 mmHg) in QW and REM. Middle-aged male TPH2-/- rats also had more frequent extreme hypertensive events (EHEs) during prolonged episodes of REM. Female TPH2-/- had normal ABP. The low and very low frequency components of systolic ABP variability were significantly higher in middle-aged male, but not female, TPH2-/- rats compared to TPH2+/+, suggesting elevated sympathetic vascular tone in male TPH2-/-. However, the hypertension of male TPH2-/- rats was not ameliorated by ganglionic blockade. Hearts and lungs of middle-aged male TPH2-/- rats were significantly heavier than those of TPH2+/+. We show that a loss of CNS 5-HT leads to high ABP only in middle-aged males during wakefulness and REM sleep, possibly due to increased vascular tone. It should be investigated whether elevated ventricular afterload associated with CNS 5-HT deficiency initiates cardiac remodeling or alters pulmonary hemodynamics.

中文翻译：

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中枢血清素对动脉血压调节作用的性别和年龄差异。

髓质血清素（5-羟色胺；5-HT）神经元投射到中枢神经系统中的多个自主神经核。缺乏 5-HT 的婴儿大鼠在安静睡眠中的动脉血压 (ABP) 较低，但尚未研究 5-HT 对成人警戒状态下 ABP 的作用。我们假设在成人中，当 5-HT 神经元活跃时，CNS 5-HT 缺乏会导致低血压，主要发生在清醒 (QW) 和非快速眼动睡眠 (NREM) 中。我们在 2-3、5-8 和 12-13 个月大时测试了雄性和雌性色氨酸羟化酶 2 敲除大鼠 (TPH2-/-)，特别是缺乏 CNS 5-HT 和野生型 (TPH2+/+) 对照. 与 TPH2+/+ 相比，5-8 和 12-13 个月大（中年）雄性 TPH2-/- 大鼠的平均动脉压在 QW 和 REM 中显着升高（~10 mmHg）。中年雄性 TPH2-/- 大鼠在 REM 长期发作期间也发生更频繁的极端高血压事件 (EHE)。女性 TPH2-/- 的 ABP 正常。与 TPH2+/+ 相比，中年雄性而非雌性 TPH2-/- 大鼠收缩期 ABP 变异性的低频和极低频成分显着更高，表明雄性 TPH2-/- 中交感神经血管张力升高。然而，雄性 TPH2-/- 大鼠的高血压并未因神经节阻滞而得到改善。中年雄性TPH2-/-大鼠的心肺明显重于TPH2+/+。我们表明，中枢神经系统 5-HT 的损失仅在中年男性清醒和快速眼动睡眠期间导致高 ABP，这可能是由于血管张力增加。