Abstract-In this study, we investigated the cardiovascular responses mediated by rostral ventrolateral medulla neurons (RVLM) in the Goldblatt hypertension model (2K-1C) treated or not treated with captopril. The actions of glutamate into the RVLM were tested, injecting glutamate (0.1 mol/L, 100 nL) and its antagonist kynurenic acid (0.02 mol/L, 100 nL). Glycine (0.5 mol/L, 100 nL) was also microinjected. Experiments were performed in male Wistar rats (weight, 250 to 300 g); 5 groups were studied: (1) 2K-1C nontreated (H, nϭ6); (2) 2K-1C treated with captopril, 10 mg/kg per day (Ht10, nϭ10); (3) 2K-1C treated with captopril, 50 mg/kg per day (Ht50, nϭ7); (4) control normotensive rats (N, nϭ7); and (5) normotensive rats treated with captopril, 50 mg/kg per day (Nt50, nϭ8). All experiments in 2K-1C were performed 6 weeks after renal surgery; captopril treatment lasted for the last 2 weeks. In urethane-anesthetized rats (1.2 g/kg IV), bilateral microinjection of glycine into the RVLM caused a depressor response; there was no difference between groups in relation to the change of variation (N: 54Ϯ2; H: 46Ϯ12; Ht10: 50Ϯ3, and Ht50: 42Ϯ7 mm Hg). Only in the H group, kynurenic acid microinjection into the RVLM caused a depressor response (H: 158Ϯ8 to 132Ϯ8 mm Hg). Glutamate response was larger in hypertensive than in normotensive rats (N: 38Ϯ2.6 and H: 55Ϯ6); no difference was observed between hypertensive groups. The data suggest that glutamate acts tonically to drive the RVLM in 2K-1C rats, and this action is modulated by endogenous angiotensin II. The increase in the glutamate actions within the RVLM may contribute to the pathogenesis of renovascular hypertension. Key Words: brain Ⅲ angiotensin Ⅲ captopril Ⅲ amino acid Ⅲ sympathetic nervous system T he rostral ventrolateral medulla (RVLM) plays a central role in neural control of the circulation. 1 Ongoing activity of premotor RVLM neurons is responsible for the generation of sympathetic vasomotor tone. Inhibition of RVLM neurons causes a large decrease in arterial blood pressure (BP) similar to that seen after total inhibition of the autonomic nervous system. 1,2 Previous studies demonstrated that microinjection into the RVLM of excitatory amino acid (EAA) receptor antagonist has no effect on basal level of BP. 3 This fact has been interpreted as suggesting that the ongoing RVLM activity is not dependent of EAA inputs to RVLM. However, we showed previously that in the Goldblatt 2-kidney, 1-clip (2K1C) model, injection of kynurenic acid (Kyn), a broadspectrum EAA receptor antagonist, into the RVLM reduced BP to the same extent as autonomic blockade. 4 A similar result was shown in SHR. 5 On the basis of these results, it was proposed that tonic actions of glutamatergic inputs to the RVLM are involved in the pathogenesis of experimental hypertension.Although there is general agreement on the importance of the renin-angiotensin system for increased BP in the early phase of renovascular hypertension, several findings suggest that the hypertensive response to angiotens...
