New York - Researchers have found that L-type calcium channel blockers (LCCBs) -- the most widely used drugs for treating hypertension -- may harm the heart as much as help it.
The study found that in rats and human cells in vitro, LCCBs cause changes in blood vessels -- known as vascular remodelling -- that reduce blood flow and increase pressure.
Examining epidemiological data, the team also found that LCCBs are associated with a greater risk of heart failure.The findings, published in the journal Proceedings of the National Academy of Sciences, suggest that care should be taken when prescribing these drugs to patients, particularly older adults and those with advanced hypertension.
"L-type calcium channel blockers are one of the most widely prescribed drugs to treat hypertension, yet we have found that these drugs may cause the same type of damage they are intended to prevent," said study researcher Mohamed Trebak from Penn State University in the US.
Trebak explained that vascular smooth muscle cells (VSMCs) make up the walls of blood vessels, where they help the vessels to control blood flow by contracting and relaxing. This activity is regulated by the concentration of calcium within the cells.
VSMCs contain numerous calcium-permeable channels to control this calcium concentration. Under conditions of hypertension, these channels allow too much calcium to enter VSMCs, which triggers the cells to undergo physiological changes, known as "remodelling," and to divide and proliferate.AThese remodelled, proliferative cells cause blood vessel walls to thicken and stiffen and blood pressure to rise.
"L-type calcium channel blockers were created to prevent this from happening. Yet, we found that these drugs also simultaneously cause remodelling and proliferation of VSMCs through another mechanism," Trebak added.
To investigate the specific mechanisms by which LCCBs affect VSMCs, the research team used optical, electrophysiological and molecular tools to examine smooth muscle cells in vitro and in rats.
The team found that calcium entry into VSMCs is mediated by stromal-interacting molecule (STIM) proteins activating ORAI calcium channels and that chronic exposure to LCCBs causes these STIM proteins to become overactive, which triggers VSMCs to proliferate.
Additionally, the researchers examined epidemiological data and found that incidences of heart failure were significantly higher in hypertensive patients treated with LCCBs than in hypertensive patients treated with other types of hypertension medications.
"Treatment with LCCBs is clinically associated with an elevated incidence of heart failure, which prompts a careful examination of the use of LCCBs during chronic hypertension where vascular remodelling is evident," said Trebak. (agency)
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