Cardiovascular regulation by -atginine in the brain of rats : Role of the brain renin-angiotensin system and nitric oxide

Abstract The effect of brain -arginine on arterial pressure was investigated by injecting - or -arginine into the cerebral ventricles of male Wistar rats that were anesthetized with urethane. Intracerebroventricular (ICV) injection of 1 μmol -arginine reduced the arterial pressure and the abdominal sympathetic nervous activity (SNA), whereas the injection of 10 μmol -arginine induced a transient pressor response and reduced both the heart rate and SNA. Although ICV injection of 1 μmol -arginine had no effect on cardiovascular function or SNA, injection of 10 μmol of this enantiomer elicited a transient pressor response, similar to that induced by 10 μmol -arginine, followed by a persistent increase in SNA. ICV pretreatment with the nitric oxide synthase inhibitor NG-monomethyl -arginine abolished the vasodepressor response and reduced the inhibition of SNA induced by ICV injection of 1 μmol -arginine; such pretreatment increased the arterial pressure, heart rate and SNA measured 30 min after ICV injection of 10 μmol -arginine. ICV pretreatment with the angiotensin II type 1 receptor antagonist CV-11974 inhibited the pressor response to 10 μmol -arginine and the first phase of the pressor response to 10 μmol -arginine. Intravenous pretreatment with the α1-adrenoreceptor blocker bunazosin hydrochlorine abolished the pressor response to 10 μmol -arginine of both phases of the pressor response to 10 μmol -arginine. Brain -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 -arginine-derived nitric oxide.