K. Yamada et al., THE EFFECT OF CENTRAL AMINO-ACID NEUROTRANSMITTERS ON THE ANTIHYPERTENSIVE RESPONSE TO ANGIOTENSIN BLOCKADE IN SPONTANEOUS HYPERTENSION, Journal of hypertension, 13(12), 1995, pp. 1624-1630
Objective: To investigate the effects of central amino acid neurons on
the antihypertensive action of a newly developed angiotensin II type
1 receptor (AT(1)) antagonist, CV 11974. Materials and methods: We mea
sured the release of various amino acids in the rostral ventrolateral
medulla using the brain microdialysis technique. A microdialysis probe
was inserted into the exposed rostral ventrolateral medulla in male s
pontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats anaes
thetized with urethane. Mean arterial pressure and the release of amin
o acids (glutamate, glycine, glutamine, taurine and gamma-aminobutyric
acid) were monitored before and after intravenous administration of C
V 11974 (5 mg/kg), nitroglycerin (5 mu g/kg per min) or vehicle. Resul
ts: In SHR, CV11974 decreased mean arterial pressure (-40 +/- 6 mmHg)
accompanied by significant increases in the release of inhibitory amin
o acids, glycine (411 +/- 83%) and gamma-aminobutyric acid (363 +/- 71
%) in the rostral ventrolateral medulla, whereas intravenous nitroglyc
erin produced a decrease in mean arterial pressure (-35 +/- 4 mmHg) wi
thout changes in amino acid release. In WKY rats, both intravenous CV
11974 and intravenous nitroglycerin produced smaller but significant d
ecreases in mean arterial pressure (CV11974, -18 +/- 5 mmHg; nitroglyc
erin, -20 +/- 7 mmHg) without change in the release of amino acids in
the rostral ventrolateral medulla. Selective perfusion of glycine or g
amma-aminobutyric acid into the rostral ventrolateral medulla caused a
larger mean arterial pressure reduction in SHR than in WKY rats. Furt
hermore, the use of a specific antagonist of glycine or of the gamma-a
minobutyric acid receptor in the rostral ventrolateral medulla attenua
ted the antihypertensive response induced by the intravenous AT(1) ant
agonist in SHR. Conclusion: The present results suggest that the relea
se of the inhibitory amino acids glycine and gamma-aminobutyric acid i
n the rostral ventrolateral medulla contributes to the depressor actio
n of this AT(1) receptor antagonist in the genetic hypertensive rat mo
del.