Ventral lamina terminalis mediates enhanced cardiovascular responses of rostral ventrolateral medulla neurons during increased dietary salt

Abstract

Increased dietary salt enhances sympathoexcitatory and sympathoinhibitory responses evoked from the rostral ventrolateral medulla (RVLM). The purpose of the present study was to determine whether neurons of the forebrain lamina terminalis (LT) mediated these changes in the RVLM. Male Sprague-Dawley rats with and without LT lesions were fed normal chow and given access to water or 0.9% NaCl for 14 to 15 days. Unilateral injection of l-glutamate into the RVLM produced significantly larger increases in renal sympathetic nerve activity and arterial blood pressure of sham rats ingesting 0.9% NaCl versus water. However, these differences were not observed between ventral LT-lesioned rats drinking 0.9% NaCl versus water. Similar findings were observed when angiotensin II or gamma-aminobutyric acid was injected into the RVLM. Interestingly, a subset of animals drinking 0.9% but with damage restricted to the organum vasculosum of the lamina terminalis did not show enhanced responses to l-glutamate or gamma-aminobutyric acid. In marked contrast, RVLM injection of l-glutamate or gamma-aminobutyric acid produced exaggerated sympathetic nerve activity and arterial blood pressure responses in animals drinking 0.9% NaCl versus water after an acute ventral LT lesion or chronic lesion of the subfornical organ. Additional experiments demonstrated that plasma sodium concentration and osmolality were increased at night in rats ingesting 0.9% NaCl. These findings suggest that neurons of the ventral LT mediate the ability of increased dietary salt to enhance the responsiveness of RVLM sympathetic neurons.

Figure 1

Schematic drawings of ventral LT lesions for rats drinking (A) water or (B) 0.9% NaCl. The lesion boundary is outlined in black; control animals had no lesion or received a directed misplaced lesion (grey). (C) Digital photomicrographs of two rostral-caudal levels of the lamina terminalis for control (i,ii) and ventral LT lesioned (iii, iv) rats. Scale bar = 500 μm. Coordinates are in reference to Bregma. Abbreviations: LV, lateral ventricle; DBB, diagonal band; AC, anterior commissure; OVLT, organum vasculosum of the lamina terminalis; MnPO, median preoptic nucleus; f, fornix; 3V, third ventricle; OC, optic chiasm

Figure 2

(A) Peak change in mean ABP and renal SNA during RVLM injection of L-glutamate in rats with chronic lesion of the ventral LT. (B) Individual examples of ABP, mean ABP, ∫renal SNA, and raw renal SNA during injection of 1.0 nmol L-glutamate. *P<0.05 Control+water vs Control+Salt, †P<0.05 Control+Salt vs Lesion+Salt

Figure 3

Peak change in mean ABP during RVLM injection of GABA in rats with chronic lesion of the ventral LT. (B) Individual examples of ABP and mean ABP during injection of 0.1 nmol GABA. *P<0.05 Control+water vs Control+Salt, †P<0.05 Control+Salt vs Lesion+Salt

Figure 4

(A) Peak change in mean ABP and renal SNA during RVLM injection of AngII in rats with chronic lesion of the ventral LT. (B) Individual examples of ABP, mean ABP, ∫renal SNA, and raw renal SNA during injection of 6 pmol AngII. *P<0.05 Control+water vs Control+Salt, †P<0.05 Control+Salt vs Lesion+Salt

Figure 5

(A) Schematic drawings of OVLT lesions for rats drinking water (dashed) or 0.9% NaCl (black). Lines indicate the lesion boundary. (B) Digital photomicrograph of OVLT lesion. Scale bar = 500 μm, Arrow indicates lesion. (C) Peak change in mean ABP and renal SNA of OVLT-lesioned and control rats during RVLM injection of (C) L-glutamate or (D) GABA *P<0.05 Control+water vs Control+Salt, †P<0.05 Control+Salt vs Lesion+Salt

Figure 6

Peak change in mean ABP and renal SNA during RVLM injection of L-glutamate in rats drinking water or 0.9% NaCl for 14 days that received (A) an acute ventral LT lesion or (B) chronic SFO lesion. *P<0.05 water vs salt for both groups. There were no differences between control vs lesion group within same diet