Cyclic GMP‐dependent vasodilatory properties of LASSBio 294 in rat aorta

The effects of LASSBio 294, a new 3,4‐methylenedioxybenzoyl‐2‐thienylhydrazone, on vascular tonus were investigated in isolated rat aortic rings. LASSBio 294 induced a concentration‐dependent relaxation of intact rat aortic rings with an inhibitory concentration (IC 50 ) of 74 μ M (95% confidence limits: 59 – 92). The mechanical removal of the endothelium abolished this effect. In aortic rings with intact endothelium the effect of 100 μ M LASSBio 294 was not altered by the pharmacological inhibition of NOS and cyclo‐oxygenase pathways with 500 μ M L ‐NAME and 10 μ M indomethacin, respectively. LASSBio 294 (100 μ M ) was able to relax aortic rings pre‐contracted with high extracellular K + (KCl 100 m M ). The relaxant effect of LASSBio 294 was fully reversed (and prevented) by the addition of 1 μ M ODQ (1H‐(1,2,4)oxadiazolo[4,3‐a]quinoxaline‐1‐one), a selective inhibitor of soluble guanylate cyclase. LASSBio 294 (100 μM) had no direct effect on PDE3 and PDE4 activities, however, it increased by 150% cyclic GMP content in aortic rings pre‐treated with 100 μ M L ‐NAME and 10 μ M indomethacin, as did 1 μ M zaprinast, a selective PDE5 inhibitor. In conclusion, LASSBio 294 induced relaxation of isolated rat aorta probably by directly increasing cyclic GMP content, possibly as a consequence of PDE5 inhibition.British Journal of Pharmacology (2002) 135 , 293–298; doi: 10.1038/sj.bjp.0704473