( ltimately the vessels thicken to the p...)Therapeutic role found for carbon monoxide

Based on CO's successful track record in helping to prevent vascular disease, Otterbein and first author Brian Zuckerbraun, MD, of the University of Pittsburgh, hypothesized that the gas might prove beneficial in treating pulmonary arterial hypertension.

To test this hypothesis, the scientists first exposed a PAH mouse model to a short, daily regimen of CO (in a modest concentration, equivalent to what a cigarette smoker might inhale) of one hour per day. As predicted, their results showed that the gas did indeed reverse PAH in the animals, resulting in the restoration of both normal pressures and heart weights (indicative of reversal of imminent heart failure).

The scientists next identified how this was happening.

"We determined that CO was exerting these effects by both arresting growth of the vessels' smooth muscle cells and inducing apoptosis, or cell death," he adds. Consequently, as the smooth muscle cells died, both the pulmonary blood vessels and right heart were restored to their normal size, what Otterbein describes as a case of "retro-remodeling."

"However, what we found most intriguing was that CO did not induce the death of all of the smooth muscle cells in the blood vessels, but rather selected out for destruction only the population that was problematic," he adds.

It was in the final arm of their study that the authors discovered how CO was able to selectively target the troublesome smooth muscle cells: It was relying on a second gas, nitric oxide (NO), for assistance.

"When we first started these experiments, we had the cells separated into two separate culture dishes ?endothelial cells in one, smooth muscle cells in the other," explains Otterbein. But, he adds, when they
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Source:Beth Israel Deaconess Medical Center