A new study has
identified a key regulator in the physiological pathway for increasing blood
pressure. This hormone, called ouabain, had been identified decades ago, but
little was known about how the steroid functioned in our bodies. Researchers from
the University of Maryland and the University of Ottawa discovered how ouabain
plays a crucial role in raising blood pressure (BP) and contributing to
hypertension (high BP).
The central
nervous system influences BP through the sympathetic nervous system by
controlling the release of several hormones. One of these hormones is
angiotensin II (Ang II), which is released by the hypothalamus. It was
previously known that increasing Ang II results in an increase of antidiuretic
hormone (ADH). ADH increases blood volume, resulting in an increased BP. However,
the pathway is more complex with several other hormones involved. Researchers
found that Ang II influences the production and release of the steroid ouabain.
In a similar way that long-term potentiation works as described in the
physiology reading for TBL #1, constant release of Ang II leads to a mechanism
involving ouabain and some additional hormones that make arterial myocytes more
sensitive to sympathetic stimulation. This leads to increased frequency of arterial
constriction and chronic hypertension. So when Ang II levels are high for a
prolonged time, circulating ouabain levels are high and lead to a reprogramming
of key ion transporters.
The study found
that in arterial myocytes, ouabain increases the expression of three membrane
pumps involved in sodium and calcium transport. Since ouabain is a steroid, it
can diffuse through the plasma and nuclear membrane and directly impact transcription
of the genes coding for these pumps. Ouabain also stays in circulation for a
long time after it is produced, which allows it to increase the expression of these
plasma membrane transport pumps by two to three-fold greater than when ouabain
is not in circulation. This change in the protein landscape of the plasma
membrane allows the myoctyes to be more easily sympathetically stimulated,
leading to contractions occurring more often in arterial smooth muscle.
With this
information on the role of ouabain in the sympathetic pathway for increasing
BP, therapeutic research can look for a way to block ouabain and its effects.
Developing a therapeutic to prevent ouabain synthesis or an antibody to bind
and inhibit this steroid should be able to improve the lives of people with
hypertension.
References
I find it interesting that in medicine we can discover "something", not know what it does for a decade or more, then all of the sudden new research informs the scientific community about that "somethings" function or role. This is a prime example of that, and a very important one at that. The identification of the role of this steroid hormone ouabain, will provide many medical personnel a better understanding about the pathogenesis of high blood pressure.
ReplyDeleteWhat you noted towards the end of your blog post, and I'm going to reiterate here, are the new drugs therapies that can now be created to specifically target ouabain. There are many patients whose hypertension medications are ineffective or have become less effective over time. Knowing that the inhibition of ouabain can provide an alternative, and potentially better treatment option for hypertension, is something that many physicians and patients will enjoy knowing about.
Lastly, I wondered about the role of ouabain and how its inhibition could affect other body functions. The research you blogged about showed that ouabain inhibition can reduce hypertension, but could ouabain inhibition also have other affects on the body? Just something to ponder.
Good point Paul, the only function I am aware of that ouabain performs is increasing blood pressure, but there definitely could be more functions yet to be identified. While we do not want to have constant high blood pressure, the ability to augment our BP is necessary to survival and you obviously want your arterial smooth muscle to still contract so that you can pump blood throughout your body. So in finding a therapeutic that inhibits ouabain’s effects, it will be crucial that a safe dose is established that decrease BP to a target range, but does not entirely inhibit all ouabain. This may be a dose that differs from person to person as some people may have higher levels of endogenous ouabain than others.
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