title: Potassium inhibits nitric oxide and adenosine arteriolar vasodilatation via K(IR) and Na(+)/K(+) ATPase: implications for redundancy in 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 mM KCl] in the absence and then in the presence of a second vasodilator (10(-7) M ADO, 10(-7) M SNAP, 10 mM 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.
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Iain R
authors.initials: IR
authors.lastname: Lamb
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Coral L
authors.initials: CL
authors.lastname: Murrant
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D006940:Hyperemia / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction; D009569:Nitric Oxide / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000254:Sodium-Potassium-Exchanging ATPase; D000241:Adenosine; D011188:Potassium