Vasomotion and underlying mechanisms in small arteries. An in vitro study of rat blood vessels

Abstract

Arteries from many vascular beds display vasomotion, i.e. rhythmic oscillations superimposed on a tonic contraction. Vasomotion has been studied for more than hundred years, but the underlying mechanisms are still not fully understood; they may even differ between vascular beds. The aim of this study was to characterize the elements and mechanisms behind vasomotion in mesenteric small arteries from rat. Isolated arteries displayed vasomotion when contracted by noradrenaline, both under isometric and pressurized conditions. The frequency (12-16 cpm) was not dependent of agonist concentration, but showed a tendency to reduce at low transmural pressures. The amplitude was maximal at half-maximal contraction and was inversely correlated to transmural pressure. The tension oscillations were associated with corresponding oscillations in membrane potential and are known to be associated with oscillations in intracellular Ca2+ concentration. The endothelium was essential for vasomotion, apparently by increasing smooth muscle cyclic GMP via the release of nitric oxide. Cyclic GMP seemed to have a permissive role for a pacemaker located in the smooth muscle cell. The influence of transmural pressure on vasomotion was also located at the smooth muscle level. Upon reduction of extracellular Ca2+, vasomotion continued as long as a tonic contraction was obtained. In contrast, pharmacological blockade of voltage-operated Ca2+ channels (VOCs) totally abolished vasomotion, even though a sustained contraction was still obtained. Inhibition of the handling of Ca2+ in the sarcoplasmic reticulum (SR) abolished the oscillations while facilitating Ca2+ release with caffeine increased the frequency. Thus, both VOCs and the SR are essential in generation of vasomotion. The findings in the present work did not support either K+ channels or Cl channels to be directly involved in the feedback system of oscillation, although some K(+)-channels had a modulating influence. However, vasomotion was immediately abolished when the electrogenic effect of the Na+,K(+)-ATPase was inhibited by ouabain. The present data indicates that vasomotion was eliminated even when the Na+,K(+)-ATPase activity was only partly reduced. It also suggests that the activity of Na+,K(+)-ATPase might be regulated by the extracellular Na+ concentration. Based on the present results, a model for the generation of vasomotion in rat mesenteric small arteries is proposed. Vasomotion is generated via an endothelium-dependent feedback system in the vascular smooth muscle. Release and uptake of Ca2+ by the SR causes changes in sub-membrane Ca2+ concentration, which modulate the (electrogenic) activity of the Na+,K(+)-ATPase. The subsequent changes in membrane potential modulate the activity of VOCs and the ensuing changes in Ca2+ inflow feed back on the SR.(ABSTRACT TRUNCATED AT 400 WORDS)