Morimoto S, Sasaki S, Miki S, Kawa T, Itoh H, Nakata T, Takeda K, Nakagawa M
Second Department of Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Br J Pharmacol. 2000 Mar;129(5):859-64. doi: 10.1038/sj.bjp.0703121.
It has been reported that neurovascular compression of the rostral ventrolateral medulla might be causally related to essential hypertension. Recently, we found that pulsatile compression of the rostral ventrolateral medulla increases sympathetic nerve activity and elevates arterial pressure via activation of glutamate receptors in rats. We also found that increases in sympathetic and cardiovascular activities by microinjection of L-glutamate into the rostral ventrolateral medulla are mediated by c-fos expression-related substance(s) following activation of the nitric oxide-cyclic GMP pathway. Herein, we investigated whether responses to pulsatile compression are mediated by local activation of the nitric oxide-cyclic GMP pathway and/or c-fos expression-related substance(s) in rats. Increases in arterial pressure (15+/-1 mmHg), heart rate (9+/-1 b.p.m.), and sympathetic nerve activity (% change: 8.5+/-1.1%) induced by pulsatile compression were partially but significantly inhibited after local microinjection of a nitric oxide synthase inhibitor, L-N(G)-nitroarginine methyl ester (8+/-2 mmHg, 1+/-1 b.p.m., 4.0+/-1.3%; P<0.05 vs compression without pretreatment) or 7-nitroindazole (7+/-2 mmHg, 2+/-1 b.p.m., 4.0+/-1. 5%; P<0.05), or a soluble guanylate cyclase inhibitor, methylene blue (9+/-1 mmHg, 4+/-1 b.p.m., 4.1+/-1.4%; P<0.05). In addition, increases in arterial pressure, heart rate, and sympathetic nerve activity by pulsatile compression were significantly reduced 6 h after microinjection of antisense oligodeoxynucleotide to c-fos mRNA (2+/-2 mmHg, 2+/-1 b.p.m., 1.0+/-1.0%; P<0.05 vs sense oligodeoxynucleotide). These results suggest that increases in sympathetic and cardiovascular activities induced by pulsatile compression of the rostral ventrolateral medulla are mediated, at least in part, by local activation of the nitric oxide-cyclic GMP pathway and c-fos expression-related substance(s) in rats.
据报道，延髓头端腹外侧区的神经血管压迫可能与原发性高血压存在因果关系。最近，我们发现对延髓头端腹外侧区进行搏动性压迫会增加大鼠的交感神经活动，并通过激活谷氨酸受体升高动脉血压。我们还发现，向延髓头端腹外侧区微量注射L-谷氨酸所引起的交感神经和心血管活动增加，是由一氧化氮-环磷酸鸟苷途径激活后与c-fos表达相关的物质介导的。在此，我们研究了大鼠对搏动性压迫的反应是否由一氧化氮-环磷酸鸟苷途径的局部激活和/或与c-fos表达相关的物质介导。在局部微量注射一氧化氮合酶抑制剂L-N(G)-硝基精氨酸甲酯（动脉血压升高8±2 mmHg、心率升高1±1次/分钟、交感神经活动变化百分比为4.0±1.3%；与未预处理的压迫相比，P<0.05）、7-硝基吲唑（动脉血压升高7±2 mmHg、心率升高2±1次/分钟、交感神经活动变化百分比为4.0±1.5%；P<0.05）或可溶性鸟苷酸环化酶抑制剂亚甲蓝（动脉血压升高9±1 mmHg、心率升高4±1次/分钟、交感神经活动变化百分比为4.1±1.4%；P<0.05）后，搏动性压迫所引起的动脉血压升高（15±1 mmHg）、心率升高（9±1次/分钟）和交感神经活动增加（变化百分比：8.5±1.1%）受到部分但显著的抑制。此外，在微量注射针对c-fos mRNA的反义寡脱氧核苷酸6小时后，搏动性压迫所引起的动脉血压、心率和交感神经活动增加显著降低（动脉血压升高2±2 mmHg、心率升高2±1次/分钟、交感神经活动变化百分比为1.0±1.0%；与正义寡脱氧核苷酸相比，P<0.05）。这些结果表明，延髓头端腹外侧区搏动性压迫所引起的交感神经和心血管活动增加，至少部分是由大鼠体内一氧化氮-环磷酸鸟苷途径的局部激活和与c-fos表达相关的物质介导的。
