New Class of Compounds May Revive Failing Hearts

Researchers have developed a new class of nitric oxide (NO) compounds called nitroxyl precursors that produce hydrogen nitrite (HNO) and in early studies appear to play a role in protecting the cardiovascular system from further damage during heart failure and in restoring function to affected organs.

When a compound called Angeli's salt, which generates HNO, was administered to normal, conscious dogs and those with heart failure, the treatment doubled the ability of the dog hearts to pump and enhanced their ability to relax between contractions. Prior research has also shown that nitroxyl precursors appear to be very good candidates to treat failing hearts characterized by pressure overload, contractile function, and delayed relaxation.

However, a main reaction of nitroxyl is dimerization. "So, compounds that release HNO at faster rates generate higher initial concentrations of it and therefore may result in HNO being consumed by the dimerization reaction, rather than being available to elicit the desired physiologic response,” explained John P. Toscano, professor in the chemistry department at the Krieger School of Arts and Sciences at Johns Hopkins University (Baltimore, MD, USA; www.jhu.edu).

Therefore, two new derivatives of nitric oxide, one a pure HNO donor and one a pure NO donor, have been tested on dogs. "This looks promising,” said Prof. Toscano. "We know that NO is an important biological molecule, and we are just beginning to learn that HNO may, in potentially very different ways, be just as important.”





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