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Potassium inhibits nitric oxide and adenosine arteriolar vasodilatation via K IR and Na + /K + ATPase: implications for redundancy in active hyperaemia
Author(s) -
Lamb Iain R.,
Murrant Coral L.
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/jp270613
Subject(s) - vasodilation , nitric oxide , chemistry , adenosine , hyperaemia , skeletal muscle , pharmacology , medicine , biochemistry , biology , blood flow , organic chemistry
Key points Multiple vasodilators have been identified as being important in matching blood flow to the metabolism of contracting skeletal muscle and it has been hypothesized that this process is governed by redundancy between vasodilators, where one vasodilator can compensate for the loss of another. In the present study, we aimed to determine whether redundancy between vasodilators exists by investigating whether vasodilators relevant to skeletal muscle contraction can inhibit the effects of other vasodilators. We show that potassium can inhibit vasodilatations induced by adenosine and nitric oxide, and also that adenosine and nitric oxide can interact in a way that changes over time. Furthermore, we show that inward rectifying potassium channels and Na + /K + ATPase are partially mechanistically responsible for the interaction between potassium and adenosine and nitric oxide. Our data provide proof of principle that vasodilators relevant to muscle contraction interact and also that redundancy may govern the processes of active hyperaemia.Abstract Redundancy, in active hyperaemia, where one vasodilator can compensate for another if the first is missing, would require that one vasodilator inhibits the effects of another; therefore, if the first vasodilator is inhibited, its inhibitory influence on the second vasodilator is removed and the second vasodilator exerts a greater vasodilatory effect. We aimed to determine whether vasodilators relevant to skeletal muscle contraction [potassium chloride (KCl), adenosine (ADO) and nitric oxide] inhibit one another and, in addition, to investigate the mechanisms for this interaction. We used the hamster cremaster muscle and intravital microscopy to directly visualize 2A arterioles when exposed to a range of concentrations of one vasodilator [10 −8 to 10 −5 m S ‐nitroso‐ N ‐acetyl penicillamine (SNAP), 10 −8 to 10 −5 m ADO, 10 and 20 m m KCl] in the absence and then in the presence of a second vasodilator (10 −7 m ADO, 10 −7 m SNAP, 10 m m KCl). We found that KCl significantly attenuated SNAP‐induced vasodilatations by ∼65.8% and vasodilatations induced by 10 −8 to 10 −6 m ADO by ∼72.8%. Furthermore, we observed that inhibition of KCl vasodilatation, by antagonizing either Na + /K + ATPase using ouabain or inward rectifying potassium channels using barium chloride, could restore the SNAP‐induced vasodilatation by up to ∼53.9% and 30.6%, respectively, and also restore the ADO‐induced vasodilatations by up to ∼107% and 76.7%, respectively. Our data show that vasodilators relevant to muscle contraction can interact in a way that alters the effectiveness of other vasodilators. These data suggest that active hyperaemia may be the result of complex interactions between multiple vasodilators via a redundant control paradigm.