Role of Nitric Oxide in Rostral Ventrolateral Medulla of Hypertensive Rats

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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.