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Contracting human skeletal muscle maintains the ability to blunt α 1 ‐adrenergic vasoconstriction during K IR channel and Na + /K + ‐ATPase inhibition
Author(s) -
Crecelius Anne R.,
Kirby Brett S.,
Hearon Christopher M.,
Luckasen Gary J.,
Larson Dennis G.,
Dinenno Frank A.
Publication year - 2015
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp270461
Subject(s) - vasoconstriction , medicine , vasodilation , phenylephrine , endocrinology , skeletal muscle , adrenergic , chemistry , cardiology , blood pressure , receptor
Key points During exercise there is a balance between vasoactive factors that facilitate increases in blood flow and oxygen delivery to the active tissue and the sympathetic nervous system, which acts to limit muscle blood flow for the purpose of blood pressure regulation. Functional sympatholysis describes the ability of contracting skeletal muscle to blunt the stimulus for vasoconstriction, yet the underlying signalling of this response in humans is not well understood. We tested the hypothesis that activation of inwardly rectifying potassium channels and the sodium–potassium ATPase pump, two potential vasodilator pathways within blood vessels, contributes to the ability to blunt α 1 ‐adrenergic vasoconstriction. Our results show preserved blunting of α 1 ‐adrenergic vasconstriction despite blockade of these vasoactive factors. Understanding this complex phenomenon is important as it is impaired in a variety of clinical populations.Abstract Sympathetic vasoconstriction in contracting skeletal muscle is blunted relative to that which occurs in resting tissue; however, the mechanisms underlying this ‘functional sympatholysis’ remain unclear in humans. We tested the hypothesis that α 1 ‐adrenergic vasoconstriction is augmented during exercise following inhibition of inwardly rectifying potassium (K IR ) channels and Na + /K + ‐ATPase (BaCl 2 + ouabain). In young healthy humans, we measured forearm blood flow (Doppler ultrasound) and calculated forearm vascular conductance (FVC) at rest, during steady‐state stimulus conditions (pre‐phenylephrine), and after 2 min of phenylephrine (PE; an α 1 ‐adrenoceptor agonist) infusion via brachial artery catheter in response to two different stimuli: moderate (15% maximal voluntary contraction) rhythmic handgrip exercise or adenosine infusion. In Protocol 1 ( n = 11 subjects) a total of six trials were performed in three conditions: control (saline), combined enzymatic inhibition of nitric oxide (NO) and prostaglandin (PG) synthesis ( l ‐NMMA + ketorolac) and combined inhibition of NO, PGs, K IR channels and Na + /K + ‐ATPase ( l ‐NMMA + ketorolac + BaCl 2 + ouabain). In Protocol 2 ( n = 6) a total of four trials were performed in two conditions: control (saline), and combined K IR channel and Na + /K + ‐ATPase inhibition. All trials occurred after local β‐adrenoceptor blockade (propranolol). PE‐mediated vasoconstriction was calculated (%ΔFVC) in each condition. Contrary to our hypothesis, despite attenuated exercise hyperaemia of ∼30%, inhibition of K IR channels and Na + /K + ‐ATPase, combined with inhibition of NO and PGs (Protocol 1) or alone (Protocol 2) did not enhance α 1 ‐mediated vasoconstriction during exercise (Protocol 1: −27 ± 3%; P = 0.2 vs . control, P = 0.4 vs . l ‐NMMA + ketorolac; Protocol 2: −21 ± 7%; P = 0.9 vs . control). Thus, contracting human skeletal muscle maintains the ability to blunt α 1 ‐adrenergic vasoconstriction during combined K IR channel and Na + /K + ‐ATPase inhibition.