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ATP‐sensitive K+ Channel Inhibition via Glibenclamide Does Not Increase Lumbar or Renal Sympathetic Nerve Discharge in Healthy Rats

ATP‐sensitive K+ (KATP) channels contribute to exercise‐induced hyperemia and O2 delivery in skeletal muscle. KATP channel inhibition via glibenclamide (GLI) increases mean arterial pressure (MAP) and reduces blood flow to the rat hindlimb during exercise: demonstrating greater reductions in oxidative compared to glycolytic muscles. Whether this control via KATP channels is mediated locally within skeletal muscle by decreased vascular hyperpolarization or alternatively by increased sympathetic nerve activity instigated within the rostral ventrolateral medulla (Guo et al. J. Pharmacol. Exp. Therapeut. 338:458–65, 2011) or other cardiovascular control centers is unknown. We hypothesized that KATP channel inhibition via intravascular infusion of GLI would increase MAP without increasing lumbar and renal sympathetic nerve discharge (SND). In 12 male anesthetized Sprague‐Dawley rats, lumbar (n=8) and renal (n=8) nerves were isolated for measurement of SND. Following 60 min stabilization after surgery, a bolus infusion of saline (CON) was administered via the femoral vein catheter and SND, MAP (n=12), and HR (n=12) were recorded for 10 min. This protocol was then used following a bolus infusion of GLI (5 mg kg−1 in ~1 mL heparinized saline). SND was calculated as percent change from baseline (ΔSND (%)). There were no significant changes in MAP, HR, or lumbar ΔSND (%) following CON (P > 0.05 for all) and only minute 8 exhibited marginally increased renal ΔSND (%) (P < 0.05). Compared to CON, GLI increased MAP (min 3–10), reduced lumbar ΔSND (%) (min 2–10; up to 47%), and reduced renal ΔSND (%) (min 2–9; up to 36%) (P < 0.05 for all). There were no significant changes in HR due to GLI (P > 0.05). These results demonstrate that KATP inhibition produces a decrease in both lumbar and renal SND likely related to increased MAP. Therefore, reductions in exercising muscle blood flow and O2 delivery following GLI do not result from enhanced sympathetic activity; supporting that vasomotor control via KATP channels is likely mediated by local vascular effects within skeletal muscle.