Excitatory amino acids in the rostral ventrolateral medulla support blood pressure in spontaneously hypertensive rats.
Injection of the excitatory amino acid (EAA) antagonist kynurenic acid (KYN) into the rostral ventrolateral medulla (RVLM) of anesthetized rats has no effect on arterial pressure. However, we recently reported that after inhibition of the caudal ventrolateral medulla, injection of KYN into the RVLM decreased arterial pressure to the same level as produced by complete inhibition of the RVLM. We have suggested that these results reflect tonically active EAA-mediated inputs to the RVLM producing both direct excitation of RVLM vasomotor neurons and indirect inhibition of these neurons. On the basis of this model, we hypothesize that the balance between these EAA-driven direct excitatory and indirect inhibitory influences on the RVLM may be altered in models of experimental hypertension. To begin to test this hypothesis, the effects of injecting KYN into the RVLM of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were compared. In chloralose-anesthetized WKY, bilateral injection of KYN into the RVLM did not alter arterial pressure, whereas similar injections in SHR reduced mean arterial pressure by approximately 40 mm Hg. After inhibition of the caudal ventrolateral medulla, which similarly increased arterial pressure in both strains, injection of KYN into the RVLM reduced mean arterial pressure to the same level as produced by autonomic blockade. These results suggest that the balance of excitatory and inhibitory influences on RVLM vasomotor neurons driven by tonically active EAA-mediated inputs to the RVLM is disrupted in SHR and may contribute to the hypertension in SHR.
Ito
S
S
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Komatsu
K
K
Tsukamoto
K
K
Sved
A F
AF
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000737:chemistry / Q000187:drug effects*; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017470:Receptors, Glutamate / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D017470:Receptors, Glutamate; D009118:Muscimol; D018698:Glutamic Acid; D007736:Kynurenic Acid