AMINO-ACID NEUROTRANSMITTERS IN HYPERTENSION

There is compelling evidence for the participation of excitatory and inhibitory amino acids in the neural regulation of blood pressure in the normotensive rat. This is most clearly evident in the neural pathways which form the baroreceptor reflex arc. Excitatory amino acids are contained in baroreceptor afferents, neurons in the nucleus tractus solitarius (NTS) and neurons in the rostral ventrolateral medulla (RVLM). Inhibitory neurons in the caudal ventrolateral medulla (CVLM) contain gamma-aminobutyric acid. Electrophysiological and pharmacological evidence indicates that amino acid neurotransmitters are critically important to the normal function of these integrative sites in the baroreceptor reflex. Spontaneously hypertensive rats (SHR) differ from Wistar Kyoto (WKY) controls in their responses to stimulation, inhibition or lesions of neurons in the baroreceptor arc. One week after baroreceptor denervation, blood pressure is elevated in WKY but not in SHR. Stimulation of the CVLM results in a greater fall in pressure in SHR than WKY, whereas injection of tetrodotoxin into the CVLM results in a smaller increase in pressure in SHR. Blockade of glutamate receptors in the spinal cord attenuates the response to stimulation of the RVLM in both SHR and WKY, but reduces resting blood pressure in SHR only. These experiments suggest that altered activity in amino acid pathways contributes to the pathogenesis of hypertension in SHR.