Tonic Excitatory Amino Acid Input to Rostral Ventrolateral Medulla in Dahl Salt-Sensitive Rats

Abstract

16 We have previously reported that tonically active excitatory amino acid (EAA) inputs to the rostral ventrolateral medulla (RVLM) excite RVLM vasomotor neurons but also indirectly inhibit RVLM vasomotor neurons, and suggested that the balance of these influences is important in the maintenance of baseline arterial pressure (AP). In anesthetized normotensive Sprague-Dawley and Wistar rats injection of the EAA receptor antagonist kynurenic acid (KYN) into the RVLM did not alter AP. In contrast, in spontaneously hypertensive rats injection of KYN into the RVLM causes a decrease in AP, suggesting that this balance of excitatory and inhibitory influences is shifted toward excitation in this model of hypertension. Increases in dietary salt intake appear to increase the responsiveness of RVLM vasomotor neurons to excitatory inputs, but does not lead to increased AP. However, in Dahl salt-sensitive (DS) rats increased dietary salt intake causes hypertension. The goal of the present study was to examine the influence of tonically active EAA inputs to the RVLM in DS rats, to test the hypothesis that the balance of tonic excitation and inhibition of RVLM vasomotor neurons tonically driven by EAA-mediated inputs to RVLM is shifted toward excitation in DS rats. DS rats (male, 10 weeks of age) fed a diet containing either 0.3% NaCl 0r 8.0% NaCl for 3 weeks were anesthetized with chloralose and the dorsal surface of the brain stem was surgically exposed to allow injections to be made into the RVLM through glass micropipettes. MAP was elevated in DS rats fed the high salt diet compared to DS rats fed the low salt diet (173±3 vs. 123±4 mm Hg, n=8, p<0.05). Bilateral injection of KYN (2.7 nmol in 100 nl) into the RVLM decreased MAP by 16±2 mm Hg in DS rats fed the low salt diet. This effect was significantly larger in DS rats fed the high salt diet (40±2 mm Hg). These data suggest that an imbalance between the excitatory and inhibitory influences tonically active EAA-mediated inputs to RVLM vasomotor neurons may contribute to the sensitivity of DS rats to salt-induced hypertension.