Last Updated: 2001-07-27 12:08:11 EDT (Reuters Health)
מתוך מדיקונטקסט
By Steven Reinberg
WESTPORT, CT (Reuters Health) – Sildenafil inhibits hypoxia-induced pulmonary hypertension, according to preliminary data published in the July 24th issue of Circulation: Journal of the American Heart Association.
Dr. Martin R. Wilkins from Hammersmith Hospital, London, and colleagues randomized 10 male volunteers to 100-mg sildenafil or placebo before having them breathe 11% oxygen for 30 minutes.
"We found that in patients receiving sildenafil, sildenafil inhibited a rise in pulmonary artery pressure, which is normally associated with that hypoxic challenge," Dr. Wilkins told Reuters Health.
Among the subjects receiving sildenafil, plasma cGMP levels were increased significantly from baseline after 30 minutes of exposure to hypoxia. The levels did not significantly increase among subjects in the placebo group. "This observation fit nicely with other observations that we have made that suggest that sildenafil, through its inhibition of phosphodiesterase 5, relaxes pulmonary resistance," Dr. Wilkins explained.
The researchers followed up their human trial with studies of long-term administration of sildenafil to normal mice and mice deficient in endothelial nitric oxide synthase (eNOS). "We found that the effects of sildenafil we saw in human subjects were continued with chronic dosing in animals," Dr. Wilkins said.
When the animals were placed in a hypoxic chamber for 3 weeks, chronic dosing with sildenafil lowered pulmonary artery pressure, and that benefit was maintained throughout the trial. In addition, Dr. Wilkins noted, sildenafil inhibited the pulmonary remodeling associated with hypoxia.
"Even the mice deficient in eNOS showed a reduction in pulmonary artery pressure, which was not as dramatic as seen with the wild-type mice, but it was a measurable response," Dr. Wilkins said.
"The most immediate beneficiaries of our results are probably people who live at high altitudes or who climb mountains," Dr. Wilkins noted. The data also suggest, he said, that sildenafil may benefit patients with pulmonary hypertension associated with COPD or heart failure.
Circulation 2001;104:424-428.
-Westport Newsroom 203 319 2700
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