Togashi H, Sakuma I, Yoshioka M, Kobayashi T, Yasuda H, Kitabatake A, Saito H, Gross S S, Levi R
First Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
J Pharmacol Exp Ther. 1992 Jul;262(1):343-7.
We had reported that the systemic administration of N omega-methyl-L-arginine (L-NMA), a specific inhibitor of nitric oxide (NO) synthesis from L-arginine (ARG), raises arterial blood pressure (BP) while paradoxically enhancing central sympathetic outflow. Cervical spinal cord transection abolishes the increase in sympathetic outflow and attenuates the pressor effect of L-NMA. Thus, in addition to lowering BP by direct vasorelaxation, NO may also act in the central nervous system to reduce vascular sympathetic tone. To test this hypothesis we have injected L-NMA directly into the central nervous system in anesthetized rats. Intracisternally (i.c.), L-NMA elicited a small pressor response accompanied by a marked increase in sympathetic renal nerve activity (RNA). In contrast, the inactive stereoisomer N omega-methyl-D-arginine had neither pressor nor neural effects. The increases in RNA and BP elicited by i.c. L-NMA were abolished by spinal cord transection at C1 to C2 and by the i.v. administration of ARG. When administered i.c., ARG also abolished the increase in RNA elicited by i.v. L-NMA and significantly attenuated the pressor response. Thus, our findings indicate that L-NMA acts centrally by an ARG-reversible mechanism in the anesthetized rat to stimulate sympathetic nerve activity. Inasmuch as centrally synthesized NO has been postulated to play a second messenger and/or neurotransmitter role, our findings suggest that one such function would be the central regulation of sympathetic outflow and hence, BP.
我们曾报道，从L-精氨酸（ARG）合成一氧化氮（NO）的特异性抑制剂Nω-甲基-L-精氨酸（L-NMA）全身给药可升高动脉血压（BP），同时反常地增强中枢交感神经传出冲动。颈髓横断可消除交感神经传出冲动的增加，并减弱L-NMA的升压作用。因此，除了通过直接血管舒张降低血压外，NO还可能在中枢神经系统中发挥作用以降低血管交感神经张力。为了验证这一假设，我们将L-NMA直接注射到麻醉大鼠的中枢神经系统中。脑池内注射（i.c.）L-NMA可引起轻微的升压反应，并伴有肾交感神经活动（RNA）显著增加。相比之下，无活性的立体异构体Nω-甲基-D-精氨酸既无升压作用也无神经效应。C1至C2水平的脊髓横断和静脉注射ARG可消除脑池内注射L-NMA引起的RNA和BP升高。静脉注射ARG时，也可消除静脉注射L-NMA引起的RNA升高，并显著减弱升压反应。因此，我们的研究结果表明，在麻醉大鼠中，L-NMA通过一种ARG可逆机制在中枢发挥作用，刺激交感神经活动。由于中枢合成的NO被认为可发挥第二信使和/或神经递质的作用，我们的研究结果表明，其中一个这样的功能可能是对交感神经传出冲动进而对血压的中枢调节。
