1. The present study has examined the possibility that one or more metabolites of glyceryl trinitrate (GTN) (i.e. glyceryl-1,2- and -1,3-dinitrate and glyceryl-1- and -2-mononitrate) may be responsible for the second phase of the biphasic relaxant curve to GTN in phenylephrine-contracted rings of rat aorta. 2. The IC50 values for the two phases of the GTN curve were 0.1 mumol/L and 12 mumols/L with the initial phase eliciting 60% of the total relaxation response. The curves for glyceryl-1,2- and -1,3-dinitrate were monophasic with IC50 values of 248 mumols/L and 110 mumols/L, respectively. The mononitrate metabolites elicited relaxant effects at concentrations greater than or equal to 1 mmol/L. 3. The induction of tolerance to GTN or pretreatment with oxyhaemoglobin (5 mumol/L) resulted in a monophasic GTN curve with IC50 values of 16 mumol/L and 18 mumol/L respectively suggesting selective abolition of responses to low concentrations of GTN with little effect on responses to high concentrations of GTN. The relaxant effects of the -1,2- and -1,3-dinitrates, like that to GTN, were essentially unaltered by GTN tolerance or oxyhaemoglobin. 4. Thus while the relaxant effects of the dinitrate metabolites possess similar properties to that of the second phase of relaxation to GTN, a role for these metabolites is unlikely since their IC50 values are 9-20-fold greater than that for the second phase of relaxation to GTN. Whether these differences are due to the 8-10-fold lower lipophilicity of the dinitrates as compared with the parent compound requires further study.
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