Magnusson Jennifer L, Emter Craig A, Cummings Kevin J
Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, Missouri.
Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri.
J Appl Physiol (1985). 2020 Dec 1;129(6):1310-1323. doi: 10.1152/japplphysiol.00414.2020. Epub 2020 Sep 10.
Medullary serotonin (5-hydroxytryptamine; 5-HT) neurons project to multiple autonomic nuclei in the central nervous system (CNS). Infant rats lacking 5-HT have low arterial blood pressure (ABP) in quiet sleep, but the role of 5-HT in ABP regulation across vigilance states in adults has not been studied. We hypothesized that in adults, CNS 5-HT deficiency leads to hypotension mainly in quiet wakefulness (QW) and non-rapid eye movement (NREM) sleep, when 5-HT neurons are active. We tested male and female tryptophan hydroxylase 2 knockout rats , specifically deficient in CNS 5-HT, and wild-type () controls at 2-3, 5-8, and 12-13 mo of age. Compared with , mean arterial pressure of 5-8- and 12-13-mo-old (middle-aged) male rats was significantly elevated (∼10 mmHg) in QW and rapid eye movement (REM) sleep. Middle-aged male rats also had more frequent extreme hypertensive events during prolonged episodes of REM sleep. Female had normal ABP. The low- and very-low-frequency components of systolic ABP variability were significantly higher in middle-aged male, but not female, rats compared with in +/+ rats, suggesting elevated sympathetic vascular tone in male -/- rats. However, the hypertension of male rats was not ameliorated by ganglionic blockade. Hearts and lungs of middle-aged male rats were significantly heavier than those of TPH2+/+ rats. 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. The role of serotonin in arterial blood pressure (ABP) regulation across states of vigilance is unknown. We hypothesized that adult rats devoid of CNS serotonin (TPH2-/-) have low ABP in wakefulness and NREM sleep, when serotonin neurons are active. However, TPH2-/- rats experience higher ABP than TPH2+/+ rats in wakefulness and REM only, a phenotype present only in older males and not females. CNS serotonin may be critical for preventing high ABP in males with aging.
延髓5-羟色胺（5-羟色胺；5-HT）神经元投射至中枢神经系统（CNS）的多个自主神经核。缺乏5-HT的幼鼠在安静睡眠时动脉血压（ABP）较低，但5-HT在成年动物不同警觉状态下ABP调节中的作用尚未得到研究。我们推测，在成年动物中，中枢神经系统5-HT缺乏主要在安静觉醒（QW）和非快速眼动（NREM）睡眠期间导致低血压，此时5-HT神经元处于活跃状态。我们对雄性和雌性色氨酸羟化酶2基因敲除大鼠（中枢神经系统特异性缺乏5-HT）以及野生型（）对照进行了测试，年龄分别为2 - 3个月、5 - 8个月和12 - 13个月。与相比，5 - 8个月和12 - 13个月大（中年）的雄性大鼠在QW和快速眼动（REM）睡眠中的平均动脉压显著升高（约10 mmHg）。中年雄性大鼠在长时间REM睡眠期间还出现更频繁的极端高血压事件。雌性大鼠的ABP正常。与+/+大鼠相比，中年雄性大鼠收缩压变异性的低频和极低频成分显著更高，而雌性大鼠则不然，这表明雄性 -/-大鼠的交感神经血管张力升高。然而，雄性大鼠的高血压并未因神经节阻断而改善。中年雄性大鼠的心脏和肺明显比TPH2+/+大鼠的重。我们发现，中枢神经系统5-HT缺乏仅在中年雄性动物清醒和REM睡眠期间导致高血压，这可能是由于血管张力增加所致。应研究与中枢神经系统5-HT缺乏相关的心室后负荷升高是否会引发心脏重塑或改变肺血流动力学。5-羟色胺在不同警觉状态下动脉血压（ABP）调节中的作用尚不清楚。我们推测，缺乏中枢神经系统5-羟色胺（TPH2-/-）的成年大鼠在5-羟色胺神经元活跃的清醒和NREM睡眠期间ABP较低。然而，TPH2-/-大鼠仅在清醒和REM睡眠时ABP高于TPH2+/+大鼠，这种表型仅在老年雄性大鼠中出现，雌性大鼠则无此现象。中枢神经系统5-羟色胺对于预防雄性动物衰老过程中的高血压可能至关重要。
