| MadSci Network: Medicine |
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, humans. 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 heart. 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 [1] http://www.escardio.org/knowledge/cardiology_practice/ejournal_vol2/vol2no34.htm [2] http://heartdisease.about.com/cs/hypertension/a/melatonin.htm [3] http://hyper.ahajournals.org/cgi/content/full/43/2/192 [4] Hypertension. 2004 Feb;43(2):192-7. Epub 2004 Jan 19 [5] http://www.aafp.org/afp/20030415/1755.html [6] http://www.madsci.org/posts/archives/mar99/922685827.Gb.r.html [7] http://www.madsci.org/posts/archives/dec98/913251351.En.r.html [8] http://www.madsci.org/posts/archives/feb99/918216625.Gb.r.html [9] http://www.madsci.org/posts/archives/mar99/920330695.Bc.r.html
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