Ito S, Komatsu K, Tsukamoto K, Sved A F
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Hypertension. 2001 Feb;37(2):687-91.
The goal of the present study was to test the hypothesis that the balance of tonic excitation and inhibition of vasomotor neurons in the rostral ventrolateral medulla (RVLM) driven by excitatory amino acid (EAA)-mediated inputs to the RVLM is shifted toward excitation in Dahl salt-sensitive (DS) rats compared with Dahl salt-resistant (DR) rats. Glutamate and the EAA antagonist kynurenic acid were microinjected into the RVLM of chloralose-anesthetized DS and DR rats maintained on diets containing either 0.3% NaCl or 8.0% NaCl. DS rats had a higher arterial pressure than DR rats, and this difference was greatly exaggerated by high dietary salt intake. Bilateral injection of kynurenic acid (2.7 nmol) into the RVLM decreased mean arterial pressure by 16+/-2 mm Hg in DS rats fed a diet containing 0.3% NaCl, and this effect was significantly larger in DS rats fed the high-salt diet (40+/-2 mm Hg). In contrast, injections of kynurenic acid into the RVLM did not significantly decrease arterial pressure in DR rats fed either diet. In DR rats, the pressor response elicited by the injection of glutamate into the RVLM was potentiated in rats fed the high-salt diet. The glutamate-evoked pressor response was greater in DS rats compared with DR rats, and the response in DS rats was not influenced by the salt content of the diet. These data suggest that tonically active EAA inputs to the RVLM may contribute to salt-sensitive hypertension in the Dahl model.
与 Dahl 盐抵抗(DR)大鼠相比,兴奋性氨基酸(EAA)介导的延髓头端腹外侧区(RVLM)血管运动神经元的紧张性兴奋和抑制平衡在 Dahl 盐敏感(DS)大鼠中向兴奋方向偏移。将谷氨酸和 EAA 拮抗剂犬尿氨酸微量注射到用含 0.3% NaCl 或 8.0% NaCl 饲料喂养的水合氯醛麻醉的 DS 和 DR 大鼠的 RVLM 中。DS 大鼠的动脉血压高于 DR 大鼠,高盐饮食会极大地加剧这种差异。向 RVLM 双侧注射犬尿氨酸(2.7 nmol)可使食用含 0.3% NaCl 饲料的 DS 大鼠平均动脉压降低 16±2 mmHg,而在食用高盐饲料的 DS 大鼠中这种作用明显更大(40±2 mmHg)。相比之下,向 RVLM 注射犬尿氨酸对食用这两种饲料的 DR 大鼠的动脉血压均无显著降低作用。在 DR 大鼠中,向 RVLM 注射谷氨酸引起的升压反应在食用高盐饲料的大鼠中增强。与 DR 大鼠相比,DS 大鼠中谷氨酸诱发的升压反应更大,且 DS 大鼠中的反应不受饲料盐含量的影响。这些数据表明,RVLM 中持续活跃的 EAA 输入可能导致 Dahl 模型中的盐敏感性高血压。