title: Development of tolerance to glyceryl trinitrate in an isolated human peripheral vein and its relation to cyclic GMP metabolism.
abstract: Human peripheral vein (v. saphena magna) was exposed in vitro to glyceryl trinitrate (GTN) 0.1 mM for 1 h. The subsequent relaxant effect of GTN (10nM-0.1 mM) on vessels contracted by serotonin (0.25 microM) was significantly reduced on vessels preexposed to GTN as compared to control vessels, indicating a development of partial tolerance as far as the vascular smooth muscle relaxant effect is concerned. The impaired relaxant effect was paralleled by a reduced increment of intracellular cyclic GMP. This is, in turn, probably a consequence of both a diminished guanylate cyclase activity and an elevated phosphodiesterase activity in the GTN-tolerant vessels. The relaxant activity as well as the level of intracellular cyclic GMP were restored in GTN-tolerant vessels by dipyridamole (5 microM), an agent with phosphodiesterase inhibiting properties.
mesh_terms: D006152:Cyclic GMP / Q000378:metabolism*; D004176:Dipyridamole / Q000494:pharmacology; D004361:Drug Tolerance; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology*
chemical_list: D004176:Dipyridamole; D006162:Guanylate Cyclase; D005996:Nitroglycerin; D006152:Cyclic GMP