Responses to ions and vasoconstrictor agents and changes of potassium fluxes in vascular smooth muscle during hypoxia.

Abstract

An inhibitory effect of hypoxia (Po2 less than 5 mmHg) on electrical and mechanical activity of the smooth muscle of the rat portal vein has been described by Hellstrand, Johansson & Norberg (1977). The present study using the sucrose gap method confirmed their finding that spontaneous activity was completely (or almost completely) abolished by the low Po2. Increased [K+]0 from 6 to 24 mM or decreased [Na+]0 from 137.5 to 76.5 mM reinitiated electrical and mechanical activity during hypoxia. If muscle activity had already been increased by 24 mM K+ or 76.5 mM Na+ solutions in the aerobic situation, switching to hypoxia caused only partial inhibition. In hypoxic solutions of such altered ionic composition a gradual increase in muscle activity with time was seen especially in the low Na+-solution. Stimulating agents such as noradrenaline, acetylcholine, 4-aminopyridine, and Ba2+ could reinitiate spike activity and contractions under hypoxic conditions. Ouabain stimulated the activity in normoxia but no effect was seen in hypoxia. Uptake and washout of 42K+ was studied. No difference in uptake was found between normoxic and hypoxic conditions. The rate of 42K+ efflux was decreased under hypoxia. A similar decrease was produced by Mn2+ (0.4 mM) which, like hypoxia abolished phasic muscle activity. In both cases the reduction in 42K+ efflux may just reflect the elimination of action potentials. It is concluded from these results that profound hypoxia exerts its inhibitory effect on the smooth muscle to a large extent through membrane mechanisms responsible for pacemaker activity or spike generation. The electrophysiological response may be secondary to change in intracellular [Na+] or [Ca2+].