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Author: Admin | 2025-04-28
Interesting, Takimoto says, because of contradictory results of early clinical trials with sildenafil for heart failure. Notably, he says, a small, single-center clinical study showed sildenafil's long-term positive effects against cardiac remodeling and classic human heart failure. But last year, results of the RELAX study — a National Institutes of Health-sponsored, 26-center U.S. and Canadian study testing sildenafil against placebo for diastolic heart failure, a difficult-to-treat type of heart failure — found essentially no benefit.To better understand the protective effects of cGMP activity, Takimoto's team focused on the tie-in with estrogen, also known to be naturally cardioprotective. Women, for example, develop heart disease much later on average than men, usually after menopause and estrogen depletion; estrogen feeds into the cGMP pathway. But this new study by Takimoto's group used sildenafil to shed more light on the process.The team used both the TAC model and an established, powerful, gene-based model of heart failure that together better reflected human heart failure, according to Takimoto. Half of the female mice his team tested had their ovaries removed, which meant these mice had minimal levels of estrogen. Both groups of female mice received sildenafil. As expected, all the mice developed cardiac remodeling, but those low in estrogen fared far worse. Treating the estrogen-low mice with supplements of the hormone, however, raised cGMP and reversed heart damage. "This tells us that estrogen critically impacts the response to sildenafil in heart failure treatment," Takimoto says.Male mice, which have naturally low amounts of estrogen, fared differently. Like the females, they had cardiac remodeling. But sildenafil alone was able to stop it.Takimoto explains the gender effect as a difference in male-female physiology: "In female mice, their normally high estrogen levels insure presence of an ongoing pool of cGMP with its protective effects. In males, however, there's no such
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