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Effect of endothelium and carbachol on α-adrenoceptor agonist stimulated uptake and efflux of 45Ca in rat isolated aorta

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Summary

Preincubation with carbachol (10 μM) did not affect basal 45Ca accumulation by rat isolated aortic segments complete with endothelium, although 45Ca accumulation was enhanced by removal of endothelium. This confirms the observation that in the presence of endothelium Ca2+ influx in rat aorta is antagonized, and indicates that the basal release of an endothelial derived factor might be sufficient to maximally antagonize basal Ca2+ influx, or alternatively that EDRF released as a result of muscarinic stimulation does not have identical effects to the factor released under basal conditions. Accumulation of 45Ca stimulated by B-HT 920 but not that stimulated by phenylephrine was antagonized in the presence of endothelium. Contractions elicited by B-HT 920 were abolished in the presence of endothelium while contractions evoked by phenylephrine were reduced by about 50%. Preincubation with 10 μM carbachol antagonized both phenylephrine (1 μM) stimulated 45Ca accumulation and contractile responses in the presence of endothelium to about the same extent. Therefore, it might be concluded that the inhibitory effect of EDRF in this tissue is due to an inhibition of stimulated Ca2+ influx. However, while addition of carbachol to tissues precontracted with phenylephrine elicited an immediate relaxation in the presence of endothelium, this relaxation could not be correlated with a reduction in tissue accumulation of 45Ca. Carbachol also antagonized the phenylephrine-induced reduction of tissue 45Ca content (i.e. efflux of Ca2+), in tissues preloaded with 45Ca. This implies that the initial endothelial-mediated relaxant effect of carbachol in precontracted tissues cannot be explained either by reduced influx or by an enhanced efflux of Ca2+ from the smooth muscle cells. Therefore, it is concluded that although EDRF mediates a reduction in agonist-induced Cat2+ uptake it also exerts other effects, one of which may be an initial redistribution of intracelllar Ca2+, resulting in a reduction in free intracellular Ca2+ levels and therefore in relaxation.

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Author notes

  1. E. Malta

    Present address: Victorian College of Pharmacy, 381 Royal Pde. Parkville, Victoria, Australia

  2. R. C. Miller

    Present address: Merrell Dow Research Institute, 16 Rue d'Ankara, F-67084, Strasbourg Cedex, France

Authors and Affiliations

  1. Laboratoire de Pharmacodynamie Moléculaire et Cellulaire (CNRS UA600), Université Louis Pasteur, B.P. 10, F-67048, Strasbourg Cedex, France

    V. Schini, E. Malta & R. C. Miller

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Schini, V., Malta, E. & Miller, R.C. Effect of endothelium and carbachol on α-adrenoceptor agonist stimulated uptake and efflux of 45Ca in rat isolated aorta. Naunyn-Schmiedeberg's Arch Pharmacol 336, 287–294 (1987). https://doi.org/10.1007/BF00172680

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  • DOI: https://doi.org/10.1007/BF00172680

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