June 2011 FMU part 2

But when nitric oxide was produced, you know, it's a gas, so it's produced by endothelial cells. And then its first function that was recognized, that it diffuses in the underlying smooth muscle, so it acts on a neighboring cell, so in a paracrine fashion. And then once nitric oxide is produced, it only stays around for about a second, much less under certain conditions.

So the question's always been, is there.

An endocrine function of nitric oxide because it's so short lived, how can it survive transport in a sea of oxyhemoglobin, which is its known scavenger, to elicit distal functions? So we've played with that question for a number of years, and in 2007.

We actually demonstrated this quite convincingly, I.

Think, through a paper that we published in the Proceedings of the National Academy of Science with Dave Leffer's group, who was then at Emory.

So we over expressed the nitric oxide.

Synthase enzyme specifically in the heart. If you subject these animals to left.

Anterior descending artery ligation and subject them.

To a heart attack, they're very protective. So there's a heart disease, very little.

Injury, they recover quite nicely and they do very well.

But what we also did in these mice. So even though nitric oxide is over expressed and overproduced, specifically in the heart, when we measured their liver and blood levels of nitric oxide, they were elevated as well. And then if we subjected these animals to hepatic ischemia, reperfusion injury, we found that there was enormous protection from injury.

For hepatic IR injury, obviously there was.

An endocrine function, because the nitric oxide that was only over expressed in the heart then spills out into the circulatory system, is transported to distal tissues, and elicits a level of protection from insult.