L-type calcium channel blockers (LCCBs) may harm the heart as much as help it and may lead to greater risk for heart failure, finds researchers at Pennsylvania State University College of Medicine. The team pointed out that the drug may cause the same type of vascular damage they are intended to prevent.
LCCBs represent a large family of drugs most widely used as cardiac antiarrhythmics, antianginal or antihypertensives. The researchers at Penn State found that in rats and human cells in vitro, LCCBs caused changes in blood vessels known as vascular remodelling that reduced the blood flow and increased pressure.
“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 Dr Mohamed Trebak, professor of cellular and molecular physiology, Penn State.
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. These remodelled, proliferative cells cause blood vessel walls to thicken and stiffen and blood pressure to rise.
However, the LCCBs which were created to prevent the remodelling and proliferation of VSMCs were found cause it through another mechanism, said Dr Trebak
Dr Trebak and his colleagues used optical, electrophysiological and molecular tools to examine smooth muscle cells in vitro and in rats to investigate the specific mechanisms by which LCCBs affect VSMCs.
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 from the Penn State clinical database 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 Dr Trebak. “Extra care should be taken when hypertensive patients present with COVID-19, as LCCBs may exacerbate their vascular damage.
The findings suggest that care should be taken when prescribing these drugs to patients, particularly older adults and those with advanced hypertension. Their results have been published in Proceedings of the National Academy of Sciences.