Study results may lead to new blood pressure-lowering medications
University of California - Irvine
A new study from the University of California, Irvine shows that compounds in both green and black tea relax blood vessels by activating ion channel proteins in the blood vessel wall.
The discovery helps explain the antihypertensive
properties of tea and could lead to the design of new blood pressure-lowering
medications.
Published in Cellular
Physiology and Biochemistry, the discovery was made by the laboratory of
Geoffrey Abbott, PhD, a professor in the Department of Physiology and
Biophysics at the UCI School of Medicine. Kaitlyn Redford, a graduate student
in the Abbott Lab, was first author of the study titled, "KCNQ5 potassium
channel activation underlies vasodilation by tea."
Results from the research revealed that two catechin-type flavonoid compounds (epicatechin gallate and epigallocatechin-3-gallate) found in tea, each activate a specific type of ion channel protein named KCNQ5, which allows potassium ions to diffuse out of cells to reduce cellular excitability.
As KCNQ5 is found in the smooth
muscle that lines blood vessels, its activation by tea catechins was also
predicted to relax blood vessels -- a prediction confirmed by collaborators at
the University of Copenhagen.
"We found
by using computer modeling and mutagenesis studies that specific catechins bind
to the foot of the voltage sensor, which is the part of KCNQ5 that allows the
channel to open in response to cellular excitation. This binding allows the
channel to open much more easily and earlier in the cellular excitation
process," explained Abbott.
Because as many as one third of the world's adult population have hypertension, and this condition is considered to be the number one modifiable risk factor for global cardiovascular disease and premature mortality, new approaches to treating hypertension have enormous potential to improve global public health.
Prior
studies demonstrated that consumption of green or black tea can reduce blood
pressure by a small but consistent amount, and catechins were previously found
to contribute to this property. Identification of KCNQ5 as a novel target for
the hypertensive properties of tea catechins may facilitate medicinal chemistry
optimization for improved potency or efficacy.
In addition to its role in controlling vascular tone, KCNQ5 is expressed in various parts of the brain, where it regulates electrical activity and signaling between neurons. Pathogenic KCNQ5 gene variants exist that impair its channel function and in doing so cause epileptic encephalopathy, a developmental disorder that is severely debilitating and causes frequent seizures.
Because catechins can cross the blood-brain barrier, discovery of their ability to activate KCNQ5 may suggest a future mechanism to fix broken KCNQ5 channels to ameliorate brain excitability disorders stemming from their dysfunction.
Tea has been
produced and consumed for more than 4,000 years and upwards of 2 billion cups
of tea are currently drunk each day worldwide, second only to water in terms of
the volume consumed by people globally. The three commonly consumed caffeinated
teas (green, oolong, and black) are all produced from the leaves of the
evergreen species Camellia sinensis, the differences arising from different
degrees of fermentation during tea production.
Black tea is
commonly mixed with milk before it is consumed in countries including the
United Kingdom and the United States. The researchers in the present study
found that when black tea was directly applied to cells containing the KCNQ5
channel, the addition of milk prevented the beneficial KCNQ5-activating effects
of tea. However, according to Abbott, "We don't believe this means one
needs to avoid milk when drinking tea to take advantage of the beneficial
properties of tea. We are confident that the environment in the human stomach
will separate the catechins from the proteins and other molecules in milk that
would otherwise block catechins' beneficial effects."
This hypothesis
is borne out by other studies showing antihypertensive benefits of tea
regardless of milk co-consumption. The team also found, using mass
spectrometry, that warming green tea to 35 degrees Celsius alters its chemical
composition in a way that renders it more effective at activating KCNQ5.
"Regardless
of whether tea is consumed iced or hot, this temperature is achieved after tea
is drunk, as human body temperature is about 37 degrees Celsius,"
explained Abbott. "Thus, simply by drinking tea we activate its
beneficial, antihypertensive properties."
This study was
supported in part by the National Institutes of Health, National Institute of
General Medical Sciences, National Institute of Neurological Disorders and
Stroke, the Lundbeck Foundation and the Danmarks Frie Forskningsfond.