Nitrosothiol and nitrate tolerance.

Our studies on Sprague-Dawley rats showed that, in aortic tissues, nitrate tolerance is accompanied by reduced production of the 1,2-glyceryl dinitrate metabolite. This reduced vascular metabolism is consistent with the view that intracellular metabolic processes occur prior to vasodilation. The individual roles of the denitrated metabolites in nitrate tolerance are still unclear. S-nitroso N-acetyl penicillamine retains its vasodilating properties toward blood vessels which have been made tolerant toward nitroglycerin. This finding is consistent with the Ignarro Nitrosothiol Hypothesis for nitrate action. Further studies are being conducted in our laboratory to determine whether nitrosothiols are indeed non-tolerance producing "nitrates" and whether they possess suitable pharmaceutical and toxicological properties for them to become therapeutic agents themselves.