Effects of intracerebroventricular leptin and orexin-A on the baroreflex control of renal sympathetic nerve activity in conscious rats fed a normal or high-fat diet.

Abstract

This study examined the effect of leptin and orexin-A on autonomic baroreflex control in conscious Wistar rats exposed to high-fat (45% fat) or normal (3.4%) diet for 4weeks. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were monitored during the generation of baroreflex gain curves and acute volume expansion (VEP). Intracerebroventricular (ICV) leptin (1μg/min) increased RSNA in the normal diet group (0.31±0.04 vs 0.23±0.03mV/s) and MAP in the high-fat diet group (115±5 vs 105±5mm Hg, P<.05). Orexin-A (50ng/min) increased RSNA, HR and MAP in the high-fat diet group (0.26±0.03 vs 0.22±0.02mV/s, 454±8 vs 417±12beats/min, 117±1 vs 108±1mm Hg) and the normal diet group (0.18±0.05 vs 0.17±0.05mV/s, 465±10 vs 426±6beats/min, 116±2 vs 104±3 mmHg). Baroreflex sensitivity for RSNA was increased during ICV leptin by 50% in the normal diet group, compared to 14% in the high-fat diet group (P<.05). Similarly, orexin-A increased baroreflex sensitivity by 56% and 50% in the high-fat and normal diet groups, respectively (all P<.05). During ICV saline, VEP decreased RSNA by 31±5% (P<.05) after 10minutes and the magnitude of this response was blunted during ICV infusion of leptin (17±2%, P<.05) but not orexin-A in the normal diet group. RSNA response to VEP was not changed during ICV leptin or orexin-A in the high-fat diet group. These findings indicate possible central roles for leptin and orexin-A in modulating the baroreflexes under normal or increased fat intake in conscious rats and potential therapeutic approaches for obesity associated hypertension.