Moderate Elevation of Extracellular $K^+$ Concentration Induces Vasorelaxation in Isolated Rat, Rabbit and Human Cerebral Arteries: Role of Na Pump and Ba-Sensitive Process

Cerebral blood vessels relax when extracellular $K^+$ concentrations $([K^+])_e$ are elevated moderately $(2{\sim}15$ mM, $K^+-induced$ vasorelaxation). We have therefore studied the underlying mechanism for this $K^+-induced$ vasorelaxation in the isolated middle cerebral arteries (MCAs). The effects of ouabain and $Ba^{2+}\;on\;K^+-induced$ vasorelaxation were examined to determine the role of sodium pump and/or Ba-sensitive process (possibly, inward rectifier K current) in the mechanism. Mulvany myograph was used to study 24 rats, 18 rabbits, and 10 humans MCAs $(216{\pm}3\;{\mu}m,\;347{\pm}7\;{\mu}m,\;and\;597{\pm}39\;{\mu}m$ in diameter when stretched to a tension equivalent to 55 mmHg). High $K^+$ (125 mM) and $PGF_{2{\alpha}}\;(1{\sim}10\;{\mu}M)$ induced concentration-dependent contractions in all 3 species, while histamine $(10{\sim}50\;{\mu}M)$ evoked contraction only in the rabbits and induced relaxation in the rats and humans. Addition of $K^+\;(2{\sim}10\;{\mu}M)$ to the control solution induced vasorelaxations. These effects were inhibited by the pretreatment with both ouabain $(10\;{\mu}M)$ and $Ba^{2+}\;(0.1{\sim}0.3\;mM)$ in the rat, but only with ouabain $(10\;{\mu}M)$ in the rabbit and human. These results suggest that $K^+-induced$ vasorelaxation occurs via the stimulation of electrogenic Na pump in the rabbit and human MCAs, while in the rat MCAs via the activation of both Na pump and Ba-sensitive process.