Using a dog model to mimic human heart failure, the team has shown that plasma endothelin levels are elevated more predictably than other hormones associated with this disease, such as renin and aldosterone. Furthermore, when healthy animals were given endothelin to equal the plasma concentration observed in the sick dogs, coronary, renal, and systemic vasoconstriction were observed.
These findings demonstrated endothelin's potency. The team's original research (W.L. Miller, et al., Journal of Clinical Investigation, 83:317-20, 1989) indicated a pharmacologic effect, says Burnett, while the subsequent work has shown endothelin to have a biologic activity at one-tenth the dosages administered in the first study.
In addition to using dog models, the team has also investigated endothelin's role in the human body. Cardiology fellow Amir Lerman presented the results of the human study this fall. The researchers found that endothelin levels were significantly elevated among patients with symptomatic atherosclerosis. "One of the ...
