Diabetes, the cause of high blood pressure?

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Abstract of the paper itself is available at:

http://tinyurl.com/6yyrh

A probable cause for high blood pressure identified - shows links

with diabetes

Study led by Mount Sinai School of Medicine researchers found a

molecule that may be a primary cause of high blood pressure and may

be a molecular link between hypertension and diabetes

A study published in this week's Proceedings of the National Academy

of Sciences identified the molecule that binds to a receptor (a

molecule on the cell surface that triggers a reaction within the

cell) in the brain that is known to regulate blood pressure and

release of insulin. Furthermore, the researchers discovered that

this molecule acts as a neurotransmitter, in that it conveys

messages throughout different regions of the brain.

" We have known for decades that when a particular receptor in the

brain is over-stimulated, blood vessels constrict and blood pressure

rises, " said Prell, PhD, Associate Professor of Pharmacology

and Biological Chemistry at Mount Sinai School of Medicine and first

author on the study. " What we didn't know was which molecule in the

body was binding to this receptor to trigger this reaction. Now that

we have identified this substance, we can begin to look at ways of

blocking its action. We also found that excessive accumulation of

this molecule in the pancreas will impair insulin release, thus it

is possible that this molecule is the long searched for link between

these two disorders. "

The researchers found that imidazole-4-acetic acid-ribotide binds to

imidazol(in)e receptors which are widespread throughout the brain,

and are abundant in the brainstem in areas critical to blood

pressure regulation. In addition, they found that when this molecule

binds to the receptor it leads to elevated blood pressure. When an

antagonist (another molecule that blocks the action of the first) is

given, imidazole-4-acetic acid-ribotide's high blood pressure effect

is inhibited.

While some causes of high blood pressure are clearly established,

the majority of cases are considered " essential hypertension, " that

is high blood pressure for which the cause is unknown. The

researchers hypothesize that elevated levels of this ribotide may

account for a major fraction of cases of essential hypertension.

In addition, imidazole-4-acetic acid-ribotide stimulates another

group of imidazol(in)e receptors which regulate insulin release.

Among natural substances in the body, this molecule is one of the

most potent releasers of insulin ever discovered. However, while low

concentrations of the ribotide stimulate insulin release and are

therefore therapeutic, much larger concentrations block release, a

condition that produces diabetes. Thus it is important that the

ribotide levels in the pancreas be well controlled.

" Many drugs used to treat hypertension, such as clonidine, appear to

act by displacing imidazole-4-acetic acid-ribotide from these

imidazol(in)e receptors which will then block the ribotide's

hypertensive effect, " said Dr. Prell. " To date these drugs have been

problematic because they act at multiple receptors and thus have

many side effects. Now that we know the endogenous molecule that

binds to imidazol(in)e receptors, we have the potential to custom

design drugs that can specifically target the ribotide-receptor

interactions to reduce blood pressure and diminish the onset of

diabetes while avoiding other side effects. "

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