Corticotropin Releasing Factor Receptors in the Rostral Ventrolateral Medulla are Required to Initiate but not Sustain Glucose‐Induced Sympathoexcitation

Abstract

Elevated glucose and insulin increase sympathetic nerve activity (SNA) through a hypothalamic paraventricular nucleus (PVN) melanocortin receptor (MCR) dependent mechanism. Corticotropin releasing factor (CRF) co‐localizes with PVN MC4R and increases arterial blood pressure when delivered into RVLM. Here, the role of RVLM CRF receptors in glucose‐induced increases of SNA was determined. First, RVLM injection of the CRF receptor antagonist astressin (10 pmol, 60 nL) was determined to prevent the pressor effect of local CRF (25 pmol, 11±2 mmHg vs. 2±0 mmHg, P<0.05). Next, effects of CRF receptor blockade on responses to systemic glucose were tested by injecting astressin bilaterally into RVLM 15 min before or 30 min after the start of glucose infusion (150 mg/kg, 10 min, IV). In control rats (n=6) that received bilateral RVLM injections of vehicle (aCSF, 60nL), lumbar (134±9%) and splanchnic (147±6%) SNA were increased (P<0.05) 45 min post glucose infusion. In rats pre‐injected with RVLM astressin (n=4), responses were significantly smaller (lumbar SNA: 109±1%, splanchnic SNA: 120±5%, P<0.05). By contrast, RVLM astressin failed to reverse SNA responses when delivered 30 min post‐infusion (n=5). We conclude that CRF receptor activation in RVLM is required to initiate the increase of SNA by elevated glucose, but ongoing CRF signaling is not required to sustain sympathetic network activity. HL102310 & 088052 (GMT)