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Title Prof. Yang In Kim of Dpt. of Physiology Identifies a New Central Mechanism for the Antihypertensive Effect of Estrogen

Hospital KU Medicine

Date 2020-12-22

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Prof. Yang In Kim of Dpt. of Physiology

 

Identifies a New Central Mechanism for the

 

Antihypertensive Effect of Estrogen

 

 

A team led by Professor Yang In Kim of Department of Physiology of Korea

 

University College of Medicine proposed a new treatment strategy for

 

hypertension by confirming the antihypertensive effect of estrogen on the central

 

nerve system.

 

 

One of the most important risk factors and causes of hypertension is excessive

 

salt intake and the incidence of salt-dependent hypertension is lower in women

 

than men. Abundant evidence indicates this is because of estrogen’s

 

antihypertensive effect by suppressing the activation of the sympathetic nervous

 

system and vasodilation. Yet, the exact mechanism is poorly understood.

 

 

In addition to the sympathetic nervous system, the neurohumoral system that is

 

highly likely to be associated with the development of salt-dependent

 

hypertension is subsumed under the central nervous system. Some of the neurons

 

that consist the system produce vasopressin which has antidiuretic and

 

vasoconstrictive effects that play a crucial role in the pathogenesis of

 

hypertension. The team hypothesized that estrogen inhibits hypertension through

 

neurons that produce vasopressin and conducted research.

 

 

In the ovariectomized female rats salt-hypertension model, when hypertension

 

was induced, an increase in blood concentration of vasopressin was similar to

 

that of male rats. However, in sham ovariectomized rats or ovariectomized rats

 

with estrogen replacement, even with hypertension inducing procedures,

 

hypertension wasn’t induced and the blood concentration of vasopressin was

 

much lower, according to the team’s research.

 

 

The team confirmed that the cause of an increase of vasopressin in blood caused

 

by hypertension inducing procedures in male rats or ovariectomized female rats

 

is inhibitory-to-excitatory-transition of GABAergic transmission in neurons. It

 

also found that estrogen administration suppresses the emergence of GABAergic

 

excitation in vasopressin neurons in ovariectomized female rats and male rats.

 

 

In addition, the team tested that the reason estrogen suppresses the emergence of

 

GABAergic excitation in vasopressin neurons is that it prevents the accumulation

 

of chloride ions in vasopressin neurons by increasing the expression of KCC2,

 

Cl⁻ extruding transporter. The team confirmed that salt-dependent hypertension

 

was remarkably alleviated when KCC2 activator was used.

 

 

“This research is significant because it presents a new target for the development

 

of antihypertensives by investigating a new central mechanism of estrogen’s

 

antihypertensive effect,” Professor Kim stated. “I hope that the results of our

 

research will lead to the development of new treatments which will give a hope

 

to many patients suffering from hypertension.”

 

 

The paper “Oestrogen inhibits salt-dependent hypertension by suppressing

 

GABAergic excitation in magnocellular AVP neurons” was published online in

 

the world-renown journal in September

 

2020.

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