Nishimura M, Takahashi H, Nanbu A, Sakamoto M, Yoshimura M
Department of Clinical Laboratory and Medicine, Kyoto Prefectural University of Medicine, Kamigyo-ku, Japan.
Am J Hypertens. 1997 Apr;10(4 Pt 1):389-96.
The effect of brain L-arginine on arterial pressure was investigated by injecting L- or D-arginine into the cerebral ventricles of male Wistar rats that were anesthetized with urethane. Intracerebroventricular (I.C.V.) injection of 1 micromol L-arginine reduced the arterial pressure and the abdominal sympathetic nervous activity (SNA), whereas the injection of 10 micromol L-arginine induced a transient pressor response and reduced both the heart rate and SNA. Although I.C.V. injection of 1 micromol D-arginine had no effect on cardiovascular function or SNA, injection of 10 micromol of this enantiomer elicited a transient pressor response, similar to that induced by 10 micromol L-arginine, followed by a persistent increase in arterial pressure and a corresponding increase in SNA. I.C.V. pretreatment with the nitric oxide synthase inhibitor N(G)-monomethyl L-arginine abolished the vasodepressor response and reduced the inhibition of SNA induced by I.C.V. injection of 1 micromol L-arginine; such pretreatment increased the arterial pressure, heart rate, and SNA measured 30 min after I.C.V. injection of 10 micromol L-arginine. I.C.V. pretreatment with the angiotensin II type 1 receptor antagonist CV-11974 inhibited the pressor response to 10 micromol L-arginine and the first phase of the pressor response to 10 micromol D-arginine. Intravenous pretreatment with the alpha1-adrenoceptor blocker bunazosin hydrochloride abolished the pressor response to 10 micromol L-arginine and both phases of the pressor response to 10 micromol D-arginine. Brain L-arginine thus appears to exert pressor actions through stimulation of the brain renin-angiotensin system and peripheral SNA. However, these actions may be attenuated by L-arginine-derived nitric oxide.
通过向用乌拉坦麻醉的雄性Wistar大鼠的脑室注射L-精氨酸或D-精氨酸,研究了脑内L-精氨酸对动脉血压的影响。脑室内(I.C.V.)注射1微摩尔L-精氨酸可降低动脉血压和腹部交感神经活动(SNA),而注射10微摩尔L-精氨酸则引起短暂的升压反应,并降低心率和SNA。虽然I.C.V.注射1微摩尔D-精氨酸对心血管功能或SNA无影响,但注射10微摩尔这种对映体可引起短暂的升压反应,类似于10微摩尔L-精氨酸诱导的反应,随后动脉血压持续升高,SNA相应增加。I.C.V.用一氧化氮合酶抑制剂N(G)-单甲基-L-精氨酸预处理可消除血管舒张降压反应,并减少I.C.V.注射1微摩尔L-精氨酸诱导的SNA抑制;这种预处理可增加I.C.V.注射10微摩尔L-精氨酸30分钟后测得的动脉血压、心率和SNA。I.C.V.用血管紧张素II 1型受体拮抗剂CV-11974预处理可抑制对10微摩尔L-精氨酸的升压反应和对10微摩尔D-精氨酸升压反应的第一阶段。静脉用α1-肾上腺素能受体阻滞剂盐酸布那唑嗪预处理可消除对10微摩尔L-精氨酸的升压反应以及对10微摩尔D-精氨酸升压反应的两个阶段。因此,脑内L-精氨酸似乎通过刺激脑肾素-血管紧张素系统和外周SNA发挥升压作用。然而,这些作用可能会被L-精氨酸衍生的一氧化氮减弱。