Safa-Tisseront V, Ponchon P, Laude D, Elghozi J L
Laboratory of Pharmacology, CNRS URA 1482, Faculty of Medicine Necker, Paris, France.
Eur J Pharmacol. 1998 Jul 10;352(2-3):247-55. doi: 10.1016/s0014-2999(98)00368-9.
A great deal of uncertainty persists regarding the exact nature of the interaction between autonomic nervous system activity and thyroid hormones in the control of heart rate and blood pressure. We now report on thyrotoxicosis produced by daily intraperitoneal (i.p.) injection of L-thyroxine (0.5 mg/kg body wt. in 1 ml of 5 mM NaOH for 5 days). Control rats received i.p. daily injections of the thyroxine solvent. In order to estimate the degree of autonomic activation in hyperthyroidism, specific blockers were administered intravenously: atropine (0.5 mg/kg), prazosin (1 mg/kg), atenolol (1 mg/kg) or the combination of atenolol and atropine. A jet of air was administered in other animals to induce sympathoactivation. Eight animals were studied in each group. The dose and duration of L-thyroxine treatment was sufficient to induce a significant degree of hyperthyroidism with accompanying tachycardia, systolic blood pressure elevation, increased pulse pressure, cardiac hypertrophy, weight loss, tachypnea and hyperthermia. In addition, the intrinsic heart period observed after double blockade (atenolol + atropine) was markedly decreased after treatment with L-thyroxine (121.5+/-3.6 ms vs. 141.2+/-3.7 ms, P < 0.01). Of the autonomic indices, vagal tone (difference between heart period obtained after atenolol and intrinsic heart period) was negatively linearly related to intrinsic heart period (r = 0.71, P < 0.05). Atenolol modified neither the heart period nor blood pressure variability in rats with hyperthyroidism and in these rats the jet of air did not significantly affect the heart period level. The thyrotoxicosis was associated with a reduction of the 0.4 Hz component of blood pressure variability (analyses on 102.4 s segments, modulus 1.10+/-0.07 vs. 1.41+/-0.06 mm Hg, P < 0.01) and prazosin was without effect on this 0.4 Hz component in these animals. These data show a functional diminution of the vascular and cardiac sympathetic tone in early experimental hyperthyroidism. The marked rise in the intrinsic heart rate could be the main determinant of tachycardia. The blood pressure elevation may reflexly induce vagal activation and sympathetic (vascular and cardiac) inhibition.
自主神经系统活动与甲状腺激素在控制心率和血压方面的相互作用的确切性质仍存在诸多不确定性。我们现在报告通过每日腹腔注射L-甲状腺素（0.5毫克/千克体重，溶于1毫升5毫摩尔/升氢氧化钠中，持续5天）所产生的甲状腺毒症。对照大鼠每日腹腔注射甲状腺素溶剂。为了评估甲状腺功能亢进时自主神经激活的程度，静脉注射特定阻滞剂：阿托品（0.5毫克/千克）、哌唑嗪（1毫克/千克）、阿替洛尔（1毫克/千克）或阿替洛尔与阿托品的组合。对其他动物给予一股气流以诱导交感神经激活。每组研究8只动物。L-甲状腺素治疗的剂量和持续时间足以诱导显著程度的甲状腺功能亢进，并伴有心动过速、收缩压升高、脉压增加、心脏肥大、体重减轻、呼吸急促和体温升高。此外，L-甲状腺素治疗后，双重阻断（阿替洛尔+阿托品）后观察到的固有心动周期明显缩短（121.5±3.6毫秒对141.2±3.7毫秒，P<0.01）。在自主神经指标中，迷走神经张力（阿替洛尔后获得的心动周期与固有心动周期之差）与固有心动周期呈负线性相关（r = 0.71，P<0.05）。阿替洛尔对甲状腺功能亢进大鼠的心动周期和血压变异性均无影响，在这些大鼠中，气流对心动周期水平也无显著影响。甲状腺毒症与血压变异性的0.4赫兹成分降低有关（对102.4秒段进行分析，模量1.10±0.07对1.41±0.06毫米汞柱，P<0.01），在这些动物中，哌唑嗪对该0.4赫兹成分无影响。这些数据表明，在早期实验性甲状腺功能亢进中，血管和心脏交感神经张力存在功能性降低。固有心率的显著升高可能是心动过速的主要决定因素。血压升高可能会反射性地诱导迷走神经激活和交感神经（血管和心脏）抑制。
