Itoh H, Buñag R D
Department of Pharmacology, College of Health Sciences and Hospital, University of Kansas Medical Center, Kansas City 66103.
Exp Gerontol. 1992;27(3):309-20. doi: 10.1016/0531-5565(92)90058-8.
Serotonergic mechanisms for baroreflex modulation could become altered with age. This possibility was explored by comparing cardiovascular and sympathetic effects elicited in 2-month- and 24-month-old rats by injecting serotonin (5-HT) directly into the nucleus tractus solitarius (NTS) which is the primary baroreflex relay station in the medulla. Ensuing decreases in mean pressure, heart rate, and renal nerve firing were significantly smaller in 24-month-old than in 2-month-old rats. By contrast, similar injections into the NTS of the vehicle alone were ineffective in both age groups. Postmortem examination of brain sections showed that NTS injection sites were equally distributed in both age groups, thereby indicating that the brain areas affected by 5-HT were identical regardless of age. Reduced sensitivity of peripheral myocardial beta-adrenergic and vascular alpha-adrenergic receptors was considered partly responsible because 5-HT injected into the NTS lowers blood pressure by decreasing sympathetic vasomotor tone and slows the heart by increasing vagal tone with reciprocal sympatho-inhibition. But since reduced adrenergic sensitivity would not account for the concurrent decrease in renal nerve firing, a more logical explanation is that the sensitivity of serotonergic mechanisms in the NTS for inhibiting blood pressure, heart rate, and renal nerve activity decreases with age.
压力反射调节的5-羟色胺能机制可能会随年龄而改变。通过比较向孤束核(NTS,它是延髓中主要的压力反射中继站)直接注射5-羟色胺(5-HT)后在2月龄和24月龄大鼠中引发的心血管和交感神经效应,来探究这种可能性。结果显示,24月龄大鼠中平均血压、心率和肾神经放电随后的降低幅度明显小于2月龄大鼠。相比之下,单独向两个年龄组的NTS注射赋形剂均无效。对脑切片的尸检显示,NTS注射部位在两个年龄组中分布相同,从而表明受5-HT影响的脑区与年龄无关。外周心肌β-肾上腺素能受体和血管α-肾上腺素能受体敏感性降低被认为是部分原因,因为注入NTS的5-HT通过降低交感缩血管张力来降低血压,并通过增加迷走神经张力并伴有交感抑制来减慢心率。但由于肾上腺素能敏感性降低无法解释肾神经放电同时减少的现象,一个更合理的解释是,NTS中抑制血压、心率和肾神经活动的5-羟色胺能机制的敏感性随年龄降低。