Salas Nilson, Terrell Mary Lee A, Summy-Long Joan Y, Kadekaro Massako
Division of Neurosurgery, The University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX 77555-0517, USA.
Brain Res. 2003 Sep 5;983(1-2):162-73. doi: 10.1016/s0006-8993(03)03052-x.
We tested the hypothesis that in spontaneously hypertensive rat (SHR) NO produced centrally influences the resting arterial blood pressure by attenuating mechanisms involving prostaglandins, angiotensin II, endothelin and sympathetic nervous system. L-NAME (200 micro g/5 micro l), an inhibitor of NO synthase, administered intracerebroventricularly (i.c.v.) to awake and freely moving rats increased mean arterial blood pressure (MABP) in a biphasic pattern: an early transient increase within 1 min and a late prolonged response starting at 45 min and persisting for the duration of experiment (180 min). The two pressor responses involve different neurochemical mechanisms and, based on their latencies, they appear to reflect different anatomical sites of action of L-NAME. The late, but not the early pressor response, was prevented by pretreatment with chlorisondamine (2.5 mg/kg, i.v.), a ganglionic blocker, indicating its dependence on the sympathetic nervous system. Both pressor responses were abolished by i.c.v. pretreatment with indomethacin (200 micro g/5 micro l, i.c.v.), an inhibitor of cyclo-oxygenase, showing that they are mediated by prostaglandin(s). In contrast, losartan (25 micro g/5 micro l), an angiotensin II AT(1) receptor antagonist, had no effect. The initial pressor response was also attenuated by pretreatment with the endothelin ET(A)/ET(B) receptor antagonist, PD 145065 (48 micro g/2 micro l, i.c.v.). Intravenous pretreatment with another ET(A)/ET(B) receptor antagonist, L-754,142 (15 mg/kg as a bolus+15 mg/kg/h for 180 min), however, attenuated both responses to L-NAME. It is possible that L-754,142 crossed the blood-brain barrier and blocked, in addition, central ET(A)/ET(B) receptors. These studies show that NO synthesized in the brain attenuates pressor mechanisms involving prostaglandin, endothelin and sympathetic nervous system, but not angiotensin II, to modulate resting arterial blood pressure.
在自发性高血压大鼠（SHR）中，中枢产生的一氧化氮（NO）通过减弱涉及前列腺素、血管紧张素II、内皮素和交感神经系统的机制来影响静息动脉血压。将一氧化氮合酶抑制剂L-NAME（200微克/5微升）脑室内注射（i.c.v.）到清醒且自由活动的大鼠体内，会使平均动脉血压（MABP）呈双相升高：在1分钟内出现早期短暂升高，在45分钟时开始出现晚期持续反应，并在实验持续时间（180分钟）内持续存在。这两种升压反应涉及不同的神经化学机制，基于它们的潜伏期，似乎反映了L-NAME不同的解剖作用部位。用神经节阻滞剂氯异吲哚胺（2.5毫克/千克，静脉注射）预处理可预防晚期而非早期的升压反应，表明其对交感神经系统的依赖性。两种升压反应均被环氧化酶抑制剂吲哚美辛（200微克/5微升，i.c.v.）脑室内预处理所消除，表明它们由前列腺素介导。相比之下，血管紧张素II AT(1)受体拮抗剂氯沙坦（25微克/5微升）没有效果。内皮素ET(A)/ET(B)受体拮抗剂PD 145065（48微克/2微升，i.c.v.）预处理也减弱了初始升压反应。然而，用另一种ET(A)/ET(B)受体拮抗剂L-754,142（15毫克/千克静脉推注+15毫克/千克/小时持续180分钟）静脉预处理减弱了对L-NAME的两种反应。有可能L-754,142穿过了血脑屏障，此外还阻断了中枢ET(A)/ET(B)受体。这些研究表明，脑内合成的NO减弱了涉及前列腺素、内皮素和交感神经系统但不涉及血管紧张素II的升压机制，以调节静息动脉血压。
