A NEW NITRIC OXIDE-GENERATING ACTIVATOR OF SOLUBLE GUANYLATE-CYCLASE WITH ANTIHYPERTENSIVE AND ANTIAGGREGATORY PROPERTIES

Effects of 2-aminoethylisothiouronium bromide, known as a radioprotect or, on human platelet soluble guanylate cyclase and on ADP-induced hum an platelet aggregation were studied. It was shown that 2-aminoethylis othiouronium bromide in Tris buffer and at certain pH values is conver ted via trans-guanidine rearrangement to mercaptoethylguanidine. The l atter contains both guanidine and SH groups which act as donor and acc eptor of nitric oxide (NO), respectively. It was demonstrated that 2-a minoethylisothiouronium bromide after its rearrangement to mercaptoeth ylguanidine can activate human platelet soluble guanylate cyclase, inh ibit ADP-induced aggregation of human platelets, and accelerate their spontaneous disaggregation. The stimulatory effect of 2-aminoethylisot hiouronium bromide is dependent on the effectiveness of its trans-guan idine rearrangement to mercaptoethylguanidine. The molecular mechanism of a hypotensive effect of 2-aminoethylisothiouronium bromide is prop osed.