Excitatory Amino Acids in the Rostral Ventrolateral Medulla Support Blood Pressure in Spontaneously Hypertensive Rats

Abstract

Abstract-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 Ϸ40 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. Key Words: brain Ⅲ hypertension, experimental Ⅲ glutamate Ⅲ neurotransmitter Ⅲ amino acid Ⅲ rats, inbred SHR T he rostral ventrolateral medulla (RVLM) is critical to the tonic and reflexive regulation of arterial blood pressure (AP). Ongoing activity of RVLM-spinal neurons is responsible for the generation of baseline sympathetic vasomotor tone, and acute inhibition of this region causes a marked decrease in AP, similar to that seen in response to cervical spinal cord transection or inhibition of the autonomic nervous system. 1,2 Previous studies demonstrated that local injection into the RVLM of excitatory amino acid (EAA) receptor antagonists has no effect on resting AP, 3-5 and this has been interpreted as indicating that RVLM neuronal activity at rest is not produced by EAA-mediated inputs to the RVLM. However, we have recently reported that although injection of kynurenic acid (KYN) into the RVLM of anesthetized rats had no effect on baseline AP, after inhibition of the caudal ventrolateral medulla (CVLM), a region that tonically inhibits the RVLM, injection of KYN into the RVLM reduced AP to the same extent as total autonomic blockade. 6 On the basis of these results, it was proposed that tonically active EAAmediated inputs to the RVLM excite RVLM vasomotor neurons and also indirectly inhibit these neurons through excitation of an inhibitory input from the CVLM. 6 Thus, we suggested that blockade of EAA receptors in the RVLM re...

Altered regulation of the rostral ventrolateral medulla in hypertensive obese Zucker rats

“…Hypertensive rat models with enhanced angiotensinergic activation of the RVLM also appear to have augmented glutamatergic tone (3,19,20). However, in the present study we found no evidence to support the notion that enhanced tonic glutamatergic inputs to the RVLM raise SNA in the OZR.…”

“…In spontaneously hypertensive rats the tonic CVLM-mediated GABAergic inhibition of the RVLM appears to be attenuated (37). Furthermore, in many hypertensive rat models, tonic activation of RVLM by glutamate and angiotensin II are augmented (9,17,18,19,20). The principle observations of the present study are that 1) inhibition of the RVLM evoked a greater decrease in MAP in OZR compared with LZR; 2) antagonism of AT 1 Fig.…”

“…The responses to losartan were monitored for 30 min based on a previous report (9) showing maximal responses required this time period. Although the hypothalamic paraventricular nucleus appears to be a source of angiotensin II to the RVLM, blockade of AT1 receptors in the RVLM does not abolish the response to manipulation of the paraventricular nucleus (19,42), rendering it an inconclusive tool for establishing effective blockade of AT1 receptors in the RVLM. In addition, losartan does not completely abolish exogenously microinjected angiotensin II (1).…”

“…In spontaneously hypertensive rats, Dahl-saltsensitive rats, and renal injury hypertensive rats, the elevated SNA is associated with an increase in the tonic activation of the RVLM by glutamate and angiotensin II (2,9,17,18,19,20). In addition, reduced tonic GABAergic inhibition of the RVLM also appears to contribute to the elevated MAP observed in spontaneously hypertensive rats (38).…”

Role of the medulla oblongata in normal and high arterial blood pressure regulation: the contribution of Escola Paulista de Medicina - UNIFESP

“…In renovascular hypertensive rats, as well as in SHRs (Ito et al 2000), Dahl salt-sensitive rats (Ito et al 2001) and rats used in an experimental model of pulsatile compression of the RVLM (Morimoto et al 1999), the blockade of excitatory amino acid receptors in the RVLM elicited profound decreases in the arterial pressure. Our hypothesis is that the increased glutamatergic activity in the RVLM seen in hypertension is in part mediated by local or circulating Ang II.…”