Central amino acids mediate cardiovascular response to angiotensin II in the rat.
To elucidate the role of the rostral ventrolateral medulla (RVLM) in cardiovascular control through the release of central amino acid neurotransmitters, experiments were performed in Sprague-Dawley (normotensive) rats and spontaneously hypertensive rats (SHR) anesthetized with urethane by using microdialysis sampling from the RVLM for determination of amino acid neurotransmitters. The baseline release of the excitatory amino acid neurotransmitter, glutamate (GLU) from the RVLM in SHR was higher and those of the inhibitory amino acid neurotransmitters, glycine (GLY), taurine (TAU), and gamma-aminobutyric acid (GABA), were lower than in normotensive rats. Microinjection of angiotensin II (ANG II) into the RVLM caused a dose-dependent increase in mean arterial pressure (MAP) and heart rate (HR), accompanied by increased release of GLU in the RVLM. In contrast, microinjection of the ANG II type 1 receptor (AT1) antagonist CV 11974 into the RVLM reduced MAP and HR, accompanied by increased release of GLY, TAU and GABA. These changes in MAP and HR after administration of ANG II or AT1 antagonist were partially blocked by the use of the corresponding antagonist of each amino acid neurotransmitter. Furthermore, these effects were more prominently seen in SHR than in normotensive rats. These results suggest that the release of amino acid neurotransmitters mediate the cardiovascular effects of the angiotensin system in the RVLM, which may be involved in the generation of hypertension in SHR.
Zhu
D N
DN
Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
Moriguchi
A
A
Mikami
H
H
Higaki
J
J
Ogihara
T
T
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000502:physiology*; D005996:Nitroglycerin / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013777:Tetrazoles / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D018377:Neurotransmitter Agents; D013777:Tetrazoles; D014665:Vasodilator Agents; D000804:Angiotensin II; D010656:Phenylephrine; D005996:Nitroglycerin; C081643:candesartan