CENTRAL AMINO-ACIDS MEDIATE CARDIOVASCULAR-RESPONSE TO ANGIOTENSIN-IIIN THE RAT

To elucidate the role of the rostral ventrolateral medulla (RVLM) in c ardiovascular control through the release of central amino acid neurot ransmitters, experiments were performed in Sprague-Dawley (normotensiv e) rats and spontaneously hypertensive rats (SHR) anesthetized with ur ethane by using microdialysis sampling from the RVLM for determination of amino acid neurotransmitters. The baseline release of the excitato ry amino acid neurotransmitter, glutamate (GLU) from the RVLM in SHR w as higher and those of the inhibitory amino acid neurotransmitters, gl ycine (GLY), taurine (TAU), and gamma-aminobutyric acid (GABA), were l ower than in normotensive rats, Microinjection of angiotensin II (ANG II) into the RVLM caused a dose-dependent increase in mean arterial pr essure (MAP) and heart rate (HR), accompanied by increased release of GLU in the RVLM, In contrast, microinjection of the ANG II type 1 rece ptor (AT(1)) antagonist CV 11974 into the RVLM reduced MAP and HR, acc ompanied by increased release of GLY, TAU and GABA, These changes in M AP and HR after administration of ANG II or AT(1) antagonist were part ially blocked by the use of the corresponding antagonist of each amino acid neurotransmitter, Furthermore, these effects were more prominent ly seen in SHR than in normotensive rats. These results suggest that t he release of amino acid neurotransmitters mediate the cardiovascular effects of the angiotensin system in the RVLM, which may be involved i n the generation of hypertension in SHR. (C) 1998 Elsevier Science Inc .