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Angiotensin AT2 Receptor Agonist: Restorative Role For Patients With Hypertension?

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Angiotensin AT2 Receptor Agonist: Restorative Role For Patients With Hypertension?
Angiotensin AT2 Receptor Agonist: Restorative Role For Patients With Hypertension?
Thomas Unger
Thomas Unger

The illusive angiotensin AT2 receptor could become an important new target for therapy in the overall care of patients with hypertension. A leading researcher in cardiovascular medical science has found that by stimulating this receptor his group discovered remarkable regenerative and anti-inflammatory effects.

MILAN—A new drug which stimulates the angiotensin AT2 receptor is showing the way forward in therapy for hypertension, even though it does not lower blood pressure. That’s according to Thomas Unger, MD PhD, Director of the Institute of Pharmacology and the Center of Cardiovascular Research at Charité Medical University in Berlin who presented data on “compound 21″—a new AT2 receptor agonist.
The agent could become a natural partner for the better-known AT1 angiotensin receptor-modulating drugs already being used for their ability to lower blood pressure.
Expression of this “illusive” receptor is normally very low, Dr Unger said, except in some organs such as the brain, adrenal gland and uterus. In an interview after his talk in Milan he explained:
“But when there is injury—ischaemic, traumatic or hypoxic—the AT2 receptor is sometimes dramatically up-regulated.” It seems to have a protective, regenerative action, and Dr Unger and his group wanted to find more about how this might be harnessed:
“We thought: if this is a beneficial system, can we not stimulate it more—and not antagonise it as we do in the case of the AT1 receptor,” he said.
Surprisingly for the focus of a presentation at Europe’s biggest conference on hypertension, this drug has no direct effect on hypertension. But Dr Unger said it could very likely find an application for improving overall regimens for treating hypertension:
“The renin-angiotensin system is so much connected to hypertension that whatever you do in this system it has some bearing on hypertension at the same time,” he said.
Indeed one of the pharmacological possibilities he put forward was to consider combining such an AT2 agonist with an AT1 antagonist in one molecule: “This would take care of the blood pressure by [means of] the antagonist, but would have beneficial protective effects from the AT2 agonist.”
Another of the actions of compound 21 noted by the Berlin researchers is that it has controlled inflammation as strongly as steroids: “The strength is in the range of corticosteroids—not as strong as dexamethazone but in the range of hydrocortisone,” Dr Unger said. Such activity, he thought, means that the compound could be useful in fields other than cardiovascular medicine—such as dermatology and rheumatology.
Neuronal regeneration was another key restorative action of compound 21 which the German team has observed in promising experiments with investigating mice recovering from spinal cord compression injury. The scientist monitored the animals’ neuronal re-growth by observing the restoration of limb movements, and they noted that they recovered faster when taking new drug:
“AT2 stimulation was very good: the animals came back to normal earlier, and they were much stronger,” Dr Unger noted.
He suggested that the era for discovering true antihypertensive drugs is over: “What we are looking for [now] are compounds that have additional effects—against atherosclerosis, thrombotic disease—and also against chronic inflammation which is at the root of so many pathologies.”



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