Abstract
High dietary salt intake increases plasma and CSF Na+ concentration to elevate sympathetic nerve activity (SNA) and arterial blood pressure (ABP). Ablation of the anterior ventral 3 rd ventricle (AV3V) region attenuates the elevation in SNA and ABP during acute and chronic salt loading. The AV3V contains numerous hypothalamic nuclei including osmosensitive neurons of the OVLT. The purpose of this study was twofold: 1) to determine whether OVLT neurons mediate the sympathetic and hypertensive effects of central salt loading and 2) to characterize the changes in SNA to different vascular beds and/or end organs. Male Sprague-Dawley rats received an intracerebroventricular (ICV) infusion of 1M NaCl (5ul over 10min) before and after lesion of AV3V (n≥4) or OVLT (n=7). ICV infusion of NaCl increased mean ABP (8.9±1.0mmHg) and lumbar SNA (26.4±3.6%) but decreased renal (-18.6±2.3%) and splanchnic SNA (-10.6±2.3%). Electrolytic lesion of the AV3V region attenuated this Na+-induced increase in ABP (8.9±1.0 vs 1.7±0.4mmHg, p=0.001) and lumbar SNA(26.4±3.6% vs 8.0±1.9%, p=0.001) but did not alter the inhibition of renal SNA (-18.6±2.3% vs -19.2±3.5%, p>0.8) and splanchnic SNA (-10.6.±2.3% vs -8.2±1.7%, p>0.4). ICV infusion of 1M NaCl produced similar increases in ABP, lumbar, renal and splanchnic SNA between control versus sham-lesion animals. Selective lesion of the OVLT attenuated the Na+-induced increase in ABP (10.4±2.0 vs 5.8±0.8mmHg, p<0.05) and lumbar SNA (31.8±3.7 vs 16.3±2.3% p<0.02). OVLT ablation also attenuated the inhibition of renal SNA (-18.2±2.6 vs -7.5±2.4%, p<0.02) and tended to lessen the inhibition of splanchnic SNA (-8.8±1.9 vs -4.0±1.1%, p=0.065). Even though both AV3V and OVLT lesions attenuated the increase in lumbar SNA and ABP in response to central Na+ load, the magnitude of the attenuation was significantly greater in AV3V versus OVLT-lesioned animals (p<0.05). Taken together, these findings suggest that acute increases in CSF Na+ activate OVLT neurons to selectively increase lumbar SNA and ABP. However, our findings also suggest that structures other than the OVLT participate in the sympathoexcitatory response to increased CSF Na+.
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