Sympathetic Neural Contributions to Vascular Control: Role of K ATP Channels

Abstract

The ATP-sensitive K+ (KATP) channel is a class of inward rectifier K+ channels that contributes to systemic basal vasomotor tone. In rats blockade of KATP channels via glibenclamide (GLI) promotes vasoconstriction thereby increasing mean arterial pressure (MAP) and decreasing renal and hindlimb skeletal muscle blood flow. We tested the hypothesis that the GLI-induced increase in vascular tone resulted, in part, from increased renal or lumbar sympathetic nerve discharge (SND). Heart rate (HR), MAP and lumbar and renal SND (direct nerve recordings) were measured in 8 male Sprague Dawley rats for 10 min following vehicle (VEH) and GLI (2.5 mg/kg i.v.). GLI increased MAP from min 2-10 compared to both baseline and VEH (peak ΔMAP at min 10: 18 ± 4 mmHg, p < 0.05) but HR was unchanged at any time point (p > 0.05). Lumbar SND was decreased from min 2-10 (peak ΔSND at min 3: -33.7 ± 5.7 %) and renal SND was decreased from min 2-9 (peak ΔSND at min 3: -36.3 ± 3.2 %) with GLI compared to VEH (p < 0.05). These data support that GLI-induced reductions in skeletal muscle and renal blood flow reflect peripheral KATP channel vascular control and decreased SND actually acts to constrain the full magnitude of the hyperemic response. Consequently, the hindlimb skeletal muscle blood flow reductions with KATP channel blockade may be underestimated in baroreflex-intact animals. Grants: HL-108328, AG-041948