The Relaxant Effect of Glyceryltrinitrate on Isolated Human Peripheral Vein and its Relation to Cyclic GMP Metabolism

Abstract

The relaxant effect of glyceryltrinitrate (GTN) on human vena saphena magna was studied in vitro. Vessels contracted by serotonin (0.25 .mu.M) and phenylephrine (0.1 mM) were relaxed to the same extent (EC50 = 10 .mu.M) by GTN, whereas in 100 mM K+-depolarized vessels the relaxation was significantly lower. The relaxant effect produced by GTN was preceded by an elevation of cyclic guanosine-3'',5''-monophosphate (cGMP). For 0.1 mM GTN there was a 3-fold increase in cGMP after 3 min. A correlation between relaxation and increase in cGMP was established. When GTN was combined with dipyridamole (5 .mu.M) the relaxant effect of GTN was significantly greater (EC50 = 0.1 .mu.M). Phosphodiesterase inhibition, as a possible mechanism behind the observed better relaxation for the combination (GTN + dipyridamole), is briefly discussed. In conclusion, the relaxant effect of GTN on isolated human vena saphena magna seems to be (i) dependent on the contractile stimuli used, (ii) increased by the addition of DIP and (iii) to be mediated via cGMP.