VASCULAR AND HEMODYNAMIC DIFFERENCES BETWEEN ORGANIC NITRATES AND NITRITES

Because nitroglycerin (NTG, an organic nitrate) and isoamyl nitrite ha ve similar chemical structures and a common mechanism of vascular rela xation (i.e., conversion to nitric oxide in vascular tissues and activ ation of guanylyl cyclase), it has often been assumed that organic nit rates and nitrites have identical pharmacologic actions. Because recen t studies have shown that the vascular enzymes responsible for nitric oxide generation from organic nitrates and nitrites are distinct, we h ypothesized that the in vitro vascular actions, in viva hemodynamic ef fects and tolerance properties (both in vitro and in vivo) would be di fferent as well, isolated blood vessel studies showed that NTG provide d more stable relaxation effects than ISAN, was more potent and caused greater in vitro vascular tolerance. Because the mechanism(s) of vasc ular tolerance in vitro may not be the same as those occurring in vivo , we also compared the left ventricular hemodynamic effects and tolera nce properties of NTG vs. isoamyl nitrite and in congestive heart fail ure rats. Constant NTG infusion (10 mu g/min) caused initial reduction s in left ventricular end-diastolic pressure of 45 to 55%, which retur ned to baseline within 10 hr (tolerance development). in contrast, iso butyl nitrite and isoamyl nitrite (45 mu g/min) caused inital reductio ns in left Ventricular end-diastatic pressure similar to NTG (42-58%), but these thermodynamic effects of organic nitrites were maintained e ven when infusions were carried out to 22 hr. These results show that organic nitrites and organic nitrates are not pharmacologically identi cal (in vitro or in vivo), and may suggest a therapeutic advantage for organic nitrites in the treatment of some cardiovascular diseases.