An approach to differentiate between noradrenaline-elicited contractile processes in the rat isolated aorta

Summary

The aim of the present study was to assess the different processes contributing to the contraction induced by noradrenaline (NA, 1 gmol/l) in the rat isolated aorta. Pretreatment with maximally effective concentrations of nifedipine or cromakalim reduced the NA-induced contraction to 80 ± 3.5% or 63 ± 2.0%, respectively, without alteration of the shape of the response. After pretreatment with Mn²⁺, NA caused a transient phasic contraction followed by a sustained tonic component, comparable to the response obtained in “Ca²⁺-free” medium. Ryanodine — in the presence of extracellular Ca²⁺ — caused a slight increase of resting tension, but did not modify the NA-induced contraction. In “Ca²⁺-free” medium the contraction elicited by NA consisted of a transient phasic and a sustained tonic component. The amplitude of the phasic contraction decreased exponentially with the time of exposure to “Ca²⁺-free” medium. The phasic component was identified as elicited by Ca²⁺ released from the sarcoplasmic reticulum (SR) by means of ryanodine. If Ca²⁺ depleted tissues (80 min in “Ca²⁺-free” solution) were exposed to Ca²⁺ in the presence of Mn²⁺ or cromakalim, the NA-induced phasic response was inhibited, suggesting that Mn²⁺ and cromakalim blocked the refilling of the store. It can be concluded that activation of α₁-adrenoceptors in the rat aorta by NA elicits Ca²⁺-entry processes which have a different sensitivity to nifedipine, cromakalim and Mn²⁺. The Ca²⁺ released from SR contributes about 20% to the overall contractile response. Our data suggest that the depleted SR can be refilled from the extracellular space via a direct cromakalim- and Mn²⁺-sensitive pathway.