News > November 15, 2007

By Claire O’Brien | Contributing writer

Researchers from the university, the National Institute of Health and several other institutions have discovered a chemical process that has opened up new possibilities for the treatment of heart attacks, stroke and sickle cell disease.

Researchers from the university, the National Institute of Health and several other institutions have discovered a chemical process that has opened up new possibilities for the treatment of heart attacks, stroke and sickle cell disease.

In an online paper published in early November, senior author and professor of physics Daniel Kim-Shapiro and senior author Mark Gladwin, the chief of the vascular medicine branch of the National Heart, Lung and Blood Institute of the NIH, explained their newfound understanding of how nitrite could be converted to nitric oxide within hemoglobin. Hemoglobin is the molecule that carries oxygen in the blood.

Kim-Shapiro has been working on hemoglobin for the past 14 years; his focus has been on sickle cell hemoglobin since he was a graduate student at UC-Berkeley. “I wanted to apply my knowledge of physics to a health-related problem, hoping I could make a difference,” he said.

Kim-Shapiro’s interest in nitric oxide began during his first year at the university during his work with Bruce King, professor of chemistry, as they studied the relationship between nitric oxide and hemoglobin and the role this relationship plays in sickle cell disease.

In 2003, in a project led by Gladwin, a discovery was made that nitrite is a vasodilator, which means it increases blood flow.

They hypothesized that hemoglobin was the agent of reducing nitrite to the vasodilator nitric oxide.

There was one small problem with their conclusion – nitric oxide reacts quickly within hemoglobin, too quickly for it to escape into the blood- steam.

“So how could nitrite be converted to nitric oxide?” Kim-Shapiro said.

A team of 17 people from several institutions and countries have been studying this problem for the last four years.

The ability of hemoglobin to convert nitrite to nitric oxide has long confounded scientists. The process is invisible to electron paramagnetic resonance spectroscopy, currently the most advanced analysis technique available.

But four years of hard work have led the team to conclude that nitric oxide gets out of the red blood cell and into the blood stream by an intermediate species dinitrogen trioxide (N2O3).

Because nitrite plays an important role in studies of health problems such as sickle cell disease, stroke and gastric diseases, among others, this discovery will help in the search for treatments.

Sickle cell anemia, a genetic disease caused by abnormal hemoglobin, currently affects millions of people throughout the world. Kim-Shapiro, who is listed as a co-inventor on a government patent for using nitrite to treat cardiovascular conditions, hopes that by increasing understanding about nitrite’s actions, his team’s research will help in the development of new and more effective therapies for patients with sickle cell anemia and other conditions.