STUDIES OF THE EFFECT OF GLYCERYL TRINITRATE AND CYCLIC-GMP ON CALCIUM TURNOVER IN BOVINE MESENTERIC-ARTERY

It was recently observed that the relaxation induced by glyceryl trinitrate (GTN) showed a biphasic concentration‐response curve; a high‐sensitivity component represented by concentrations < 1 nM and a low‐sensitivity component represented by concentrations > 1 nM. The effect of two glyceryl trinitrate concentrations (0.1 nM and 1 μM) were tested on the uptake of 45Ca2+ to tissue pieces of bovine mesenteric arteries (BMA) as well as on the uptake of 45Ca2+ to a microsomal preparation of BMA. The effect of GTN and 8‐Br‐cGMP was also studied on the IP3‐induced release of Ca2+ from the microsomal preparation preloaded with 45Ca2+. The influence of IP3 and GTN on the activity of Ca2+‐ATPase in the microsomal preparation was tested as well. The phenylephrine‐stimulated uptake of Ca2+ to tissue pieces of BMA was significantly reduced by the high GTN‐concentration (1 μM) but not by the lower concentration. The uptake of Ca2+ to the microsomal preparation was significantly stimulated by the two GTN‐concentrations tested, as well as by 8‐Br‐cGMP (0.1 mM). The calcium release induced by IP3 (1 μM) from the microsomal preparation was inhibited by both the low and the high GTN‐concentration and by 8‐Br‐cGMP (0.1 mM). The Ca2+‐ATPase activity was stimulated by both GTN‐concentrations tested while it was inhibited by IP3. It is concluded that GTN is able to induce a reduction of the free intracellular Ca2+ by several mechanisms, which are of importance for the relaxation represented by the high‐affinity component. The low‐affinity component in addition reduces the inflow of Ca2+ over the plasma membrane. 1990 Nordic Pharmacological Society