Antagonism of relaxing responses to nitrovasodilators by cyanide in rabbit isolated aortic preparation

Effect of sodium cyanide on the relaxing response (decrease of intraluminal pressure) to sodium nitroprusside, sodium nitrite, nitric oxide and human atrial natriuretic peptide (HANP) was investigated in isolated rabbit aortic preparations in vitro. Cyanide 1 microM approximately 1 mM produced relaxation in norepinephrine (NE) 1 microM-contracted aortic preparation in a concentration dependent manner. Cyanide 100 microM, which was administered approximately 8 min before NE addition, depressed the relaxing response to nitroprusside 0.1 microM in NE 1 microM-contracted aortic preparation. The relaxing responses to nitric oxide 0.3 and 3.3 microM were slightly, but concentration-dependently depressed by cyanide 1-100 microM, which was administered 6-10 min before nitric oxide addition, in NE 1 microM-contracted aortic preparations. Cyanide 100 microM and 1 mM, which was administered 4-10 min after nitroprusside 0.1 microM, reversed the nitroprusside-induced relaxation in NE 1 microM contracted aortic preparation. Namely, relaxing response of NE-contracted aortic preparation to cyanide was converted into contractile response in the presence of nitroprusside. Similar reversal phenomena of the responses to cyanide 100 microM and 1 mM were also observed in the presence of sodium nitrite 0.1 microM or nitric oxide 3.3 microM, but those were less extent than that of nitroprusside 0.1 microM. On the contrary, the relaxing response to cyanide 100 microM was unaffected by pretreatment with HANP 0.37 nM. These findings may indicate that cyanide inhibits soluble guanylate cyclase activated by nitroprusside, sodium nitrite or nitric oxide through interaction with nitric oxide and heme binding site of the enzyme.