MadSci Network: Medicine

Re: Why would a sleeping aid on daphnia decrease the heart rate?

Date: Mon Feb 28 12:36:03 2005
Posted By: Jens Peter Bork, M.D., Internal Medicine, Erlangen University Hospital
Area of science: Medicine
ID: 1101445304.Me

Dear Monika, 

I am afraid that I may not be able to answer your question entirely to your
satisfaction – in the „Re:“ line of your question, you refer to herbal
medicines slowing down the heart rate of small crustaceans of the genus
Daphnia. In the main body of your question, you ask in more general terms:
Why would sleeping supplements slow down the heart rate – and that; I take
it, refers to the hear rate of those who take these medications: namely,

It is relatively easy to answer the question for humans: These sleeping
supplements slow down heart rate because they make us sleep! There is a
natural circadian rhythm in blood pressure (BP) and heart rate (HR) in
humans (as in almost any animal): It is higher during the waking hours than
during sleep. You can easily find this out tethering a human to a 24 h
ambulatory blood pressure monitor that takes a measurement of blood
pressure and heart rate every 15 min. Interestingly, the loss of the „night
trough“, that is, the lowering of blood pressure and heart during the
night, is considered an early, surreptitious sign of hypertension and
should be treated with antihypertensive medication (you find an article on
this in [1], together with the typical BP/HR profile of a healthy person).

From that you can plausibly infer that anything that makes us sleep will
also lower BP and HR. The mechanism of that action is situated in the
brain. It would take too much neurobiology to explain the mechanism of the
wake/sleep cycle completely within the scope of this answer. Let us just
say that several regulatory centers in the brain (among them, the ascending
reticular formation in the brainstem) can, on  a very general level, induce
sleep and waking patterns of activity in the rest of the brain. The brain
then induces several physiological changes typical for sleep in the rest f
the body. These include a relaxation of muscle tone, a reduction in BP and
HR, as well as relatively deep, slow and regular breathing. The point about
the reduction of BP and HR is that this achieved by a relatively simple
mechanism, namely the deactivation of the sympathetic and the activation of
the parasympathetic branches of the peripheral vegetative nervous system.
You probably know already that the sympathetic side of the vegetative
nervous system is the one that makes us ready for all kinds of hot action:
fleeing, fighting, sharp vision, quick reflexes, all kinds of stress. and
that the parasympathetic branch is what makes us ready for keeping
ourselves in good shape: Digesting food; slowing us down; putting us to
sleep; moving our bowels and emptying our bladders. 

So while all sorts of substances will make us sleepy by all sorts of
mechanisms in the brain, all these different mechanism boil down to the
same (well, similar) effects in the rest of the body – and among these are
lowered BP and HR. These two phenomena are, if you will, the universal
„output“ of a brain putting itself and the rest of the body to sleep. 

I searched for evidence of the two medications you name – melatonin and
valerian root – for direct effects on the heart, and I did not find any –
which is the case in a lot of  drug affecting sleep patterns. A lot of them
tend to exert their effects exclusively via the brain, at least if taken at
normal doses. However, I found one article describing Melatonin’s
BP/HR-lowering properties in terms of its specific action on a particular
structure in the brain: the suprachiasmatic nucleus, which is an important
„switchboard“ in the chain of command from the brain to the peripheral
vegetative nervous system [2; an article for the general reader; 3 the
original article, also available for free; 4; the formal reference]. A nice
overview of the evidence concerning valerian root’ action on the brain  you
find in [5]. This article is abundantly referenced for your  further
research. It makes no mention of any direct effects of valerian root on the

Now, as for Daphnia... I must admit that I never worked with this species
as a student, and my knowledge of animal biology (other than humans, of
course) is not very deep. So, if you are interested in specific aspects of
Daphnia, try these pages [6-9] in MadSci dealing with the effects of other
drugs on Daphnia heart rate. They also tell a lot about the general biology
of Daphnia’s heart rate regulation. If you want a detailed discussion of
your herbals on Daphnia, I suggest you resubmit your question to one of the
general biologists of MadSci. I do, however, have some general hints for
you which I hope are helpful: First of all, if you came across the heart
rate-lowering effects of your herbals in your own experiments, be very
careful to check if your conditions were well controlled: For example,
herbal extracts often contain alcohol, which is known to slow down the
heart rate in Daphnia (see [6] and [9]); second, if you dissolved tablets
or something like that, these can also contain all kinds substances having
an effect on your little animal’s heart rate. So you would have to control
your experiments very tightly: Using the complete drug preparation vs. the
complete drug preparation minus the drug itself – not easy to do, sometimes. 

Assuming your data pass this test, I suspect that the solution to your
question is quite similar to the one I described for humans: We are all
animals, after all, and some basic, important regulatory mechanisms in
animal physiology haven’t changed that much since evolution invented them.
There is a „higher neural center“ in these animals, too (the cardiac
ganglion) which steers heart action, and I would assume that this ganglion
is susceptible to the actions of the herbals you mentioned in a similar way
as the cells of the brain. I doubt that the effect of these medications on
HR in Daphnia result from any direct action on the heart. Just to be clear:
Let me stress that the exact mechanisms of action for a lot of medications
have never been elucidated. Valerian root extract, for example, contains a
number of substances that are thought to be important in its sedative
effects. One of them is gamma-amino butyric acid (GABA), whose molecular
action is quite well-characterized (this you can read in any good General
Pharmacology book in your institution’s library), but the effects of others
are often not. So of course, a direct action on the heart is entirely
possible, although I favor the ganglion hypothesis. 

So, if you found these effects under well controlled conditions, were able
to reproduce them, you might indeed have found something entirely new doing
your experiments – in that case, congratulations!

And never stop exploring!
Yours truly 
Jens Peter Bork

[4]	Hypertension. 2004 Feb;43(2):192-7. Epub 2004 Jan 19

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