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 less than 1 nM and a low-sensitivity component represented by concentrations greater than 1 nM. The effect of two glyceryl trinitrate concentrations (0.1 nM and 1 microM) 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 microM) 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 microM) 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.
Ahlner
J
J
Department of Clinical Pharmacology, University Hospital, Linköping, Sweden.
Axelsson
K L
KL
Karczewski
P
P
Andersson
R G
RG
D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002417:Cattle; D006152:Cyclic GMP / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007295:Inositol Phosphates / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology*
D007295:Inositol Phosphates; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D005996:Nitroglycerin; D006152:Cyclic GMP; D002118:Calcium