Role of Nitric Oxide in Rostral Ventrolateral Medulla of Hypertensive Rats

研究了一氧化氮（NO）在高血压大鼠延髓吻侧腹外侧（RVLM）中的作用。在RVLM中微量注射NO供体或l -精氨酸可引起降压反应，自发性高血压大鼠（SHR）的降压反应明显大于正常WKY大鼠。脑室内输注l -精氨酸2周不能改变shr的动脉压。长期使用一氧化氮合酶抑制剂L-NAME治疗的大鼠脑室内注射一氧化氮供体产生比正常血压大鼠更大的抑制反应。l - name处理的大鼠对RVLM微注射l -谷氨酸或血管紧张素II的升压反应增强。口服血管紧张素II型1受体拮抗剂TCV-116的慢性降压治疗可改善SHR RVLM对l -谷氨酸的增强应激反应。上述结果提示，慢性全身性NO合成酶抑制的SHR和高血压大鼠中枢神经系统，尤其是RVLM的l -精氨酸-NO系统受损，可能参与了这些动物模型中高血压的发病机制。然而，在SHR的中枢神经系统中，一氧化氮的底物l -精氨酸的缺乏似乎不太可能。NO也可能影响RVLM中l -谷氨酸和血管紧张素II的作用。因此，一氧化氮在心血管中枢调节和高血压发病中起重要作用。

Role of nitric oxide (NO) in the rostral ventrolateral medulla (RVLM) of hypertensive rats was examined.1. Microinjection of NO donor or L-arginine into the RVLM elicited depressor response, which was significantly greater in spontaneously hypertensive rats (SHR) than in normotensive WKY rats.2. Intracerebroventricular infusion of L-arginine for 2 weeks failed to alter arterial pressure of SHR.3. Intracerebroventricular injection of NO donor produced greater depressor response in the rats that were chronically treated with an NO synthase inhibitor L-NAME than in control normotensive rats. Pressor response to L-glutamate or angiotensin II microinjected into the RVLM was augmented in the L-NAME-treated rats.4. Chronic antihypertensive treatment with oral administration of angiotensin II type 1 receptor antagonist TCV-116 improved the augmented pressor responsiveness to L-glutamate in the RVLM of SHR.These results suggest that L-arginine-NO system is impaired in the central nervous system, especially in the RVLM, of SHR and hypertensive rats with chronic systemic NO synthase inhibition, which may contribute to the pathogenesis of hypertension in these animal models. However, the deficiency of L-arginine, the substrate of NO, seems unlikely in the central nervous system of SHR. NO may also have an influence on the actions of L-glutamate and angiotensin II in the RVLM. Thus, NO plays an important role in the central cardiovascular regulation and in the pathogenesis of hypertension.