Glyceryl trinitrate inhibits phosphatidylinositol hydrolysis and protein kinase C activity in bovine mesenteric artery.
The effect of glyceryl trinitrate (GTN) on relaxation, cGMP levels, phosphorylase a activity, phosphatidylinositol hydrolysis and protein kinase C activity was studied on isolated bovine mesenteric arteries (BMA). Two concentrations of GTN were tested, 0.1 nM representing a high affinity component and 1 microM representing a low affinity component of the GTN induced relaxation of BMA, giving a relaxation of 20% and 60% and a 2-fold and 5-fold increase in cGMP, respectively. Phosphatidylinositol hydrolysis and protein kinase C activity were significantly, and to the same extent, reduced at both concentrations tested, whereas the phosphorylase a activity was significantly reduced at the higher concentration only, which might indicate a reduction of the free intracellular Ca2+-concentration at high concentrations of GTN. It is concluded that a therapeutically relevant concentration (0.1 nM) of GTN induces relaxation and an increase in cGMP in bovine mesenteric arteries. The relaxation seems to be associated with an inhibition of phosphatidylinositol hydrolysis and a reduction of the protein kinase C activity.
Ahlner
J
J
Department of Clinical Pharmacology, University Hospital, Linköping, Sweden.
Axelsson
K L
KL
Karlsson
J G
JG
Andersson
R G
RG
D000818:Animals; D002417:Cattle; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D008638:Mesenteric Arteries / Q000201:enzymology*; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D006005:Phosphorylases / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D010656:Phenylephrine; D006005:Phosphorylases; D011493:Protein Kinase C; D005996:Nitroglycerin; D006152:Cyclic GMP