Differential Control of Vascular Tone and Heart Rate by Different Amino Acid Neurotransmitters in the Rostral Ventrolateral Medulla of the Rat

Abstract

1. To test the hypothesis that a central mechanism may play a role in the minimal reflex tachycardia noted in response to peripheral converting enzyme inhibition, we compared the effects of intravenous (i.v.) ceronapril (CER) with nitroglycerin (NTG) on neurotransmitter release in the rostral ventrolateral medulla (RVLM), using an in vivo microdialysis method in pentobarbital anaesthetized rats. 2. CER (0.1 mg/kg, i.v.) caused a progressive decrease in glutamate (GLU) release (CER 65 +/- 7% vs NTG 83 +/- 3% of each baseline at 140 min, P < 0.05) and attenuated the increase in glycine (GLY) release (CER 100 +/- 8% vs NTG 122 +/- 9%, P < 0.05). 3. Prevention of blood pressure reduction due to i.v. CER by concomitant infusion of a subpressor dose of angiotensin II (AII) attenuated the progressive reduction of GLU release (87 +/- 4%, P < 0.05 compared with NTG group), whereas GLY release was not affected (106 +/- 5%, NS compared with NTG group). 4. Perfusion of GLU into this area at approximately physiological concentrations resulted in a sustained tachycardia with an attenuation of the depressor effect of i.v. CER and perfusion of GLY solely lowered blood pressure. 5. These results demonstrate that i.v. converting enzyme inhibitor reduces the release of GLU in the RVLM, which was specifically caused by reducing circulating AII, without any effect on GLY release, thus resulting in the reduction of blood pressure with minimal effect on the heart rate.

Nervous Kidney

“…Prevention of the reduction in arterial pressure with intravenous administration of Ang II also prevented the decrease in glutamate release. 35 There is strong evidence to indicate that circulating Ang II can increase peripheral sympathetic nerve activity and that this can be influenced by physiological alterations in the level of activity of the endogenous renin-angiotensin system (ie, alterations in dietary sodium intake). A major central nervous system site of action whereby circulating Ang II increases peripheral sympathetic nerve activity is the AP; an additional site is the SFO.…”

Neurotransmission Alterations in Central Cardiovascular Control in Experimental Hypertension

“…In addition, intravenous administration of an angiotensin-converting enzyme inhibitor caused a decrease in glutamate release in the RVLM [34,35]. All these data support the idea that there is an interaction between circulating Ang II and glutamatergic drive to the RVLM.…”

“…Other evidence supporting an increase of glutamatergic inputs to the RVLM in response to Ang II has been provided by studies using microdialysis, in which intravenous infusion of Ang II at a very low rate over a period of several hours caused a significant increase in glutamate release in the RVLM [34,35]. In addition, intravenous administration of an angiotensin-converting enzyme inhibitor caused a decrease in glutamate release in the RVLM [34,35].…”

Mecanismos Fisiológicos E Fisiopatológicos Determinantes Da Atividade Vasomotora Simpática

“…Em estudo prévio desenvolvido em nosso laboratório, demonstrou-se que na HA renovascular há um aumento da atividade vasomotora simpática em parte por uma ação tônica de receptores glutamatérgicos localizados na RVLM, o bloqueio desses receptores produz queda da PA em ratos hipertensos renovasculares sem afetar os níveis tensionais em ratos controles 21 . Trabalhos que relacionam a infusão de Ang II e a conseqüente liberação de glutamato na RVLM têm sido desenvolvidos e os resultados favorecem a hipó-tese de que a hipertonia glutamatérgica em resposta ao aumento crônico de Ang II pode ser um mecanismo importante no aumento do SNS e da PA 22,23 . Outro recente achado em nosso laboratório foi que o bloqueio glutamatérgico central resulta numa menor resposta pressora a Ang II administrada perifericamente, sobretudo, quando baixas doses do peptídeo são administradas.…”