PT  - JOURNAL ARTICLE
AU  - John Anthony Bauer
AU  - Tim Nolan
AU  - Ho-Leung Fung
TI  - Vascular and Hemodynamic Differences between Organic Nitrates and Nitrites
DP  - 1997 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 326--331
VI  - 280
IP  - 1
4099  - http://jpet.aspetjournals.org/content/280/1/326.short
4100  - http://jpet.aspetjournals.org/content/280/1/326.full
SO  - J Pharmacol Exp Ther1997 Jan 01; 280
AB  - Because nitroglycerin (NTG, an organic nitrate) and isoamyl nitrite have similar chemical structures and a common mechanism of vascular relaxation (i.e., conversion to nitric oxide in vascular tissues and activation of guanylyl cyclase), it has often been assumed that organic nitrates and nitrites have identical pharmacologic actions. Because recent studies have shown that the vascular enzymes responsible for nitric oxide generation from organic nitrates and nitrites are distinct, we hypothesized that the in vitrovascular actions, in vivo hemodynamic effects and tolerance properties (both in vitro and in vivo) would be different as well. Isolated blood vessel studies showed that NTG provided more stable relaxation effects than ISAN, was more potent and caused greater in vitro vascular tolerance. Because the mechanism(s) of vascular tolerance in vitro may not be the same as those occurring in vivo, we also compared the left ventricular hemodynamic effects and tolerance properties of NTG vs. isoamyl nitrite and in congestive heart failure rats. Constant NTG infusion (10 μg/min) caused initial reductions in left ventricular end-diastolic pressure of 45 to 55%, which returned to baseline within 10 hr (tolerance development). In contrast, isobutyl nitrite and isoamyl nitrite (45 μg/min) caused inital reductions in left ventricular end-diastolic pressure similar to NTG (42–58%), but these hemodynamic effects of organic nitrites were maintained even when infusions were carried out to 22 hr. These results show that organic nitrites and organic nitrates are not pharmacologically identical (in vitro orin vivo), and may suggest a therapeutic advantage for organic nitrites in the treatment of some cardiovascular diseases. The American Society for Pharmacology and Experimental Therapeutics