CARDIOVASCULAR REGULATION BY L-ARGININE IN THE BRAIN OF RATS - ROLE OF THE BRAIN RENIN-ANGIOTENSIN SYSTEM AND NITRIC-OXIDE

The effect of brain L-arginine on arterial pressure was investigated b y injecting L- or D-arginine into the cerebral ventricles of male Wist ar rats that were anesthetized with urethane. Intracerebroventricular (ICV) injection of 1 mu mol L-arginine reduced the arterial pressure a nd the abdominal sympathetic nervous activity (SNA), whereas the injec tion of 10 mu mol L-arginine induced a transient presser response and reduced both the heart rate and SNA. Although ICV injection of 1 mu mo l D-arginine had no effect on cardiovascular function or SNA, injectio n of 10 mu mol of this enantiomer elicited a transient presser respons e, similar to that induced by 10 mu mol L-arginine, followed by a pers istent increase in arterial pressure and a corresponding increase in S NA. ICV pretreatment with the nitric oxide synthase inhibitor N-G-mono methyl L-arginine abolished the vasodepressor response and reduced the inhibition of SNA induced by ICV injection of 1 mu mol L-arginine; su ch pretreatment increased the arterial pressure, heart rate, and SNA m easured 30 min after ICV injection of 10 mu mol L-arginine. ICV pretre atment with the angiotensin II type 1 receptor antagonist CV-11974 inh ibited the presser response to 10 mu mol L-arginine and the first phas e of the presser response to 10 mu mol D-arginine. Intravenous pretrea tment with the alpha(1)-adrenoceptor blocker bunazosin hydrochloride a bolished the presser response to 10 mu mol L-arginine and both phases of the presser response to 10 mu mol D-arginine. Brain L-arginine thus appears to exert presser actions through stimulation of the brain ren in-angiotensin system and peripheral SNA. However, these actions may b e attenuated by L-arginine-derived nitric oxide. (C) 1997 American Jou rnal of Hypertension, Ltd.