Effect of glyceryltrinitrate and 8-Br-cGMP on tension and phosphorylase a activity in vascular smooth muscle.
The aim of the present study was to examine the effect of glyceryltrinitrate (GTN) and 8-Br-cGMP on tension and cytosolic calcium concentration in pre-contracted bovine mesenteric arteries (BMA). The activity of glycogen phosphorylase a was used as a measure of the cytosolic calcium concentration. The activity of this enzyme is regulated by the cytosolic calcium concentration and/or cAMP. Since the cAMP level was not found to be affected by GTN-treatment, the use of phosphorylase a activity to monitor changes in the cytosolic calcium concentration can be justified. The vessels were contracted with phenylephrine (10 microM) or 100 mM K+-depolarization, which caused an increase in phosphorylase a activity. Addition of 1 microM GTN to the phenylephrine-contracted vessels resulted in a 3-4-fold rise in intracellular cGMP level, which was accompanied by a large decrease in tension and phosphorylase a activity. The K+-depolarized vessels, on the other hand, were largely resistant to the relaxant action of GTN, and there was only a slight reduction of the phosphorylase a activity. In phenylephrine-contracted vessels, made tolerant to GTN by incubation at elevated pH in the presence of GTN (0.44 mM), no changes in tension and phosphorylase a activity were seen after stimulation with a test dose of GTN (1 microM). The cGMP response was also markedly blunted in the tolerant vessels. Relaxation of phenylephrine-contracted BMA induced by 8-Br-cGMP (0.5 mM) was also accompanied by a reduction in phosphorylase a activity.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007537:Isometric Contraction; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D005996:Nitroglycerin / Q000494:pharmacology*; D010762:Phosphorylase a / Q000378:metabolism*; D006005:Phosphorylases / Q000378:metabolism*
C016276:8-bromocyclic GMP; D000242:Cyclic AMP; D010762:Phosphorylase a; D006005:Phosphorylases; D005996:Nitroglycerin; D006152:Cyclic GMP; D002118:Calcium