Long-acting calcium channel blocker, azelnidipine, increases endothelial nitric oxide synthase in the brain and inhibits sympathetic nerve activity
Long-acting calcium channel blocker, azelnidipine, increases endothelial nitric oxide synthase in the brain and inhibits sympathetic nerve activity
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DOI：
10.1080/10641960601096745
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发表时间：
2007-01-01
影响因子：
12.3
通讯作者：
Sunagawa, Kenji
中科院分区：
文献类型：
--
作者：
Kimura, Yoshikuni;Hirooka, Yoshitaka;Sunagawa, Kenji
中枢神经系统中的一氧化氮（NO）抑制交感神经活动，从而降低血压。然而，目前尚不清楚口服降压治疗是否会改变NO合成酶（NOS）的表达，特别是在大脑中的表达，以及NOS表达的变化如何影响交感神经活动。阿泽尼地平是一种新近开发的长效二氢吡啶类钙通道阻滞剂，不会引起调压反射性心动过速。本研究的目的是确定阿泽尼地平降压治疗是否会改变脑内内皮NOS （eNOS）、神经元NOS （nNOS）或诱导NOS （iNOS）的表达，以及NOS的变化如何影响交感神经活动。Azelnidipine （20 mg/kg/day）或hydralazine （20 mg/kg/day）口服给药30天，用于卒中易发自发性高血压大鼠（SHRSP）。采用尾袖法测量血压和心率。测量尿去甲肾上腺素排泄量作为交感神经活动的标志。Western blot检测eNOS、nNOS或iNOS在大脑（皮质、小脑、下丘脑和脑干）、心脏和主动脉中的表达水平。两组血压降低的程度相似。心率在肼治疗组增加，但在阿泽地平治疗组没有变化。尿去甲肾上腺素排泄仅在肼治疗组显著增加。azelnidipine治疗显著增加脑、心脏和主动脉的eNOS表达水平，但未改变nNOS或iNOS表达水平。用肼嗪治疗未改变NOS的表达水平。这些结果表明，azelnidipine抗高血压治疗可以减弱反射性交感神经激活，并提高大脑、心脏和主动脉中eNOS的表达水平。
Nitric oxide (NO) in the central nervous system inhibits sympathetic nerve activity, thereby decreasing blood pressure. It is unknown, however, whether orally administered antihypertensive treatment alters NO synthase (NOS) expression, particularly in the brain, and how changes in NOS expression affects sympathetic nerve activity. Azelnidipine, a recently developed long-acting dihydropyridine calcium channel blocker, does not cause baroreflex-induced tachycardia. The aim of the present study was to determine whether antihypertensive treatment with azelnidipine alters endothelial NOS (eNOS), neuronal NOS (nNOS), or inducible NOS (iNOS) expression in the brain, and how changes in NOS affect sympathetic nerve activity. Azelnidipine (20 mg/kg/day) or hydralazine (20 mg/kg/day) was orally administered for 30 days in stroke-prone spontaneously hypertensive rats (SHRSP). Blood pressure and heart rate were measured by the tail cuff method. Urinary norepinephrine excretion was measured as a marker of sympathetic nerve activity. Western blot analysis was performed to examine eNOS, nNOS, or iNOS expression levels in the brain (cortex, cerebellum, hypothalamus, and the brain stem), heart, and aorta. The extent of blood pressure reduction was similar between the two groups. Heart rate increased in the hydralazine-treated group but did not change in the azelnidipine-treated group. Urinary norepinephrine excretion was significantly increased only in the hydralazine-treated group. Treatment with azelnidipine significantly increased eNOS expression levels in the brain, heart, and aorta, but did not alter nNOS or iNOS expression levels. Treatment with hydralazine did not change any of the NOS expression levels. These results suggest that antihypertensive treatment with azelnidipine attenuates reflex-induced sympathetic activation and enhances eNOS expression levels in the brain as well as in the heart and aorta.