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 Pt 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.
与盐敏感型(DS)大鼠相比,在兴奋性氨基酸(EAA)介导的延髓头端腹外侧区(RVLM)输入驱动下,盐抵抗型(DR)大鼠RVLM中血管运动神经元的紧张性兴奋和抑制平衡向兴奋方向偏移。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饮食喂养的氯醛糖麻醉的DS和DR大鼠的RVLM中。DS大鼠的动脉压高于DR大鼠,高盐饮食摄入极大地加剧了这种差异。向RVLM双侧注射犬尿氨酸(2.7 nmol)使摄入含0.3%NaCl饮食的DS大鼠平均动脉压降低16±2 mmHg,在高盐饮食喂养的DS大鼠中这种作用显著更大(40±2 mmHg)。相比之下,向RVLM注射犬尿氨酸对摄入任何一种饮食的DR大鼠的动脉压均无显著降低作用。在DR大鼠中,向RVLM注射谷氨酸引发的升压反应在高盐饮食喂养的大鼠中增强。与DR大鼠相比,DS大鼠中谷氨酸诱发的升压反应更大,且DS大鼠中的反应不受饮食盐含量的影响。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。