An approach to differentiate between noradrenaline-elicited contractile processes in the rat isolated aorta |
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Authors: | Peter Koch Bob Wilffert Doris Wilhelm Thies Peters |
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Affiliation: | (1) Janssen Research Foundation, Raiffeisenstrasse 8, D-4040 Neuss 21, Federal Republic of Germany |
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Abstract: | 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 1-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.Send offprint requests to: B. Wilffert at the above address |
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Keywords: | Noradrenaline Rat aorta Ca2+-entry blockers Ryanodine Cromakalim |
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