AI Article Synopsis
- Doxazosin, an antihypertensive drug, is linked to a higher risk of congestive heart failure and induces apoptosis (cell death) in cardiomyocytes.
- The drug blocks hERG K(+) channels, which are plasma membrane receptors, specifically affecting human embryonic kidney (HEK) cells that express these channels.
- The study reveals that doxazosin's binding to hERG may initiate apoptotic processes, suggesting a new understanding of how some drugs could contribute to heart failure.
Article Abstract
The antihypertensive drug doxazosin has been associated with an increased risk for congestive heart failure and cardiomyocyte apoptosis. Human ether-a-go-go-related gene (hERG) K(+) channels, previously shown to be blocked by doxazosin at therapeutically relevant concentrations, represent plasma membrane receptors for the antihypertensive drug. To elucidate the molecular basis for doxazosin-associated pro-apoptotic effects, cell death was studied in human embryonic kidney cells using three independent apoptosis assays. Doxazosin specifically induced apoptosis in hERG-expressing HEK cells, while untransfected control groups were insensitive to treatment with the antihypertensive agent. An unexpected biological mechanism has emerged: binding of doxazosin to its novel membrane receptor, hERG, triggers apoptosis, possibly representing a broader pathophysiological mechanism in drug-induced heart failure.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2239015 | PMC |
| http://dx.doi.org/10.1016/j.ejphar.2007.10.051 | DOI Listing |
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