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Medical Forum / General / General / August 2006Free radicals, Oxidants/Anti-oxidants
Hello, I just want to know that whether Free radicals, Oxidants & Anti-oxidants can effect vascular tone or act as vasoconstrictor or vasodilator? Best wishes > Hello, > [quoted text clipped - 3 lines] > > Best wishes One of the major controllers of vascular tone is nitric oxide (NO), a free radical. NO production by the endothelial cells which line the blood vessels causes the vessels to relax, thus opening up further and allowing for greater blood flow. NO is what is produced by drugs such as nitroglycerin and amyl nitrate for heart disease. These drugs are used to treat heart diseases where blood flow to the heart is limited. By dilating the blood vessels, these drugs increase oxygen delivery to the heart. NO gas itself is given to preemies and other pulmonary-compromised individuals, as it improves oxygen absorption by increasing blood flow through the lungs and other tissues - my lab has published a number of papers on this subject, here's some of the newer ones: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra ctPlus&list_uids=14739156&query_hl=2&itool=pubmed_docsum http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra ctPlus&list_uids=12925459&query_hl=2&itool=pubmed_docsum http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra ctPlus&list_uids=12897804&query_hl=2&itool=pubmed_docsum http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra ctPlus&list_uids=12707049&query_hl=2&itool=pubmed_docsum http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra ctPlus&list_uids=12039841&query_hl=2&itool=pubmed_docsum NO acts over very short distances (paracrine), so overdosing on antioxidants wouldn't do much to the effects of NO (most NO activity appears to be between contacting cells). Other oxidants may play a role in your vascular tone, but to a lesser extent. For example, the production of superoxide (O2-) appears to be required for some immune cells to get out of the blood, and this molecule appears to act like NO - as a signaling molecule which acts between cells in contact with each other. The migration of immune cells out of the blood alters several elements of the vasculature, including vascular tone and permeability. Superoxide could potentially be involved in this, either directly or indirectly. But the jury is still out on that. AFAIK, there is no direct link between antioxidant levels and vascular tone. But that said, I'd bet that there is a correlation between exogenous antioxidant levels and vascular tone - as most of the exogenous antioxidants are plant derived. If you've got a lot of these antioxidants in your blood it means you're eating your fruits and veggies. Which means you'll have lower blood pressure then people not eating their fruits and veggies. And blood pressure is paritally determined by vascular tone. So there may be a correlation, but I suspect it is (would be?) indirect, and largely due to differences in diet rather then direct effects of antioxidants. Bryan > > Hello, > > [quoted text clipped - 50 lines] > > Bryan Bryan, thanks. Iron is also considered as pro-oxidant. How its levels can effect vascular tone? Can oxidants and free radicals, in common, be related to the vessels to relax or dilate and anti-oxidant to the vessels to contract or constrict? > Bryan, thanks. > > Iron is also considered as pro-oxidant. How its levels can effect > vascular tone? Iron is complicated, as it's involved in the transport of oxygen around the body. If you loose a lot of blood, or are anemic (both of which result in a loss of iron), you'll tend to loose vascular tone as you're body will try to increase blood flow to tissues no longer getting sufficient oxygen. AFAIK, the pro-oxidant effects of iron don't really factor into this. > Can oxidants and free radicals, in common, be related to the vessels to > relax or dilate and anti-oxidant to the vessels to contract or > constrict? I don't think we know the answer to that. I doubt there is a direct link with antioxidants; most NO signaling appears to occur cell-to-cell, so its hard to see how anti-oxidants could interfere with that process to any great extent. One oxidant (nitric oxide) is most definitely involved in allowing vessels to relax. Whether or not other oxidants do the same is not known. We don't even have a good handle on how NO does what it does... Bryan > > Hello, > > [quoted text clipped - 50 lines] > > Bryan Can there may be some relation in between oxidants/free radicals, in common, and vasodilation or muscles relaxtions whereas antioxidants with vaso-constriction? What are the symptoms of excessive free radicals an Can taking antioxidants be harmful? > Can there may be some relation in between oxidants/free radicals, in > common, and vasodilation or muscles relaxtions whereas antioxidants > with vaso-constriction? We don't know. One oxidant, NO, is involved in relaxing blood vessles. AFAIK, no antioxidents have ever been implicated in causing vessles to contract (this usually occurs in response to other chemical signals like prostiglandins and leukotrienes). > What are the symptoms of excessive free radicals We're just beginning to understand this field, and the answer is "it varies". In the lungs, excessive free radicals have been assocaited with a disease known as COPD - a disease of smokers, and is 100% lethal. Excessive oxidative stress may result in cancer and other diseases. But there is a flip-side; in infected tissue immune cells produce large amounts of radicals which they use to kill bacteria. So it's probably an issue of how much oxidants are produced, where they are produced, which oxidants are produced (they're not all equal in their destructiveness), and most importantly, how long they are produced for. > an Can taking > antioxidants be harmful? Yes. Any substance - be it water, lead, salt, steak, or whatever - is toxic at some level. This is true for antioxidants as well. Many commonly used antioxidants are readily exerted if we eat too much (people who overdose on vitamin c essentially are making expensive pee), but cases of harmful overdosing certantly are possible and occur occasionally. Bryan > > Can there may be some relation in between oxidants/free radicals, in > > common, and vasodilation or muscles relaxtions whereas antioxidants [quoted text clipped - 13 lines] > But there is a flip-side; in infected tissue immune cells produce large > amounts of radicals which they use to kill bacteria. More blood flow may be needed to transport more macrophases in interstitial compartments in case of infection/inflammation. NO is known to promote it. May be other oxidants/free radical also doing that. > So it's probably an issue of how much oxidants are produced, where they > are produced, which oxidants are produced (they're not all equal in [quoted text clipped - 12 lines] > > Bryan Thanks. >>> Can there may be some relation in between oxidants/free radicals, in >>> common, and vasodilation or muscles relaxtions whereas antioxidants [quoted text clipped - 14 lines] > More blood flow may be needed to transport more macrophases in > interstitial compartments in case of infection/inflammation. Although inflammation does increase blood flow to the damaged areas there is no evidence that this improves the recruitment of immune cells such as macrophage. Indeed, immune cells regularly and efficiently move into all sorts of tissues without the benefit of inflammation or increased blood flow. Macrophages are a good example - they exist normally in our tissues, and to keep this population of cells present they need to be continually replaced. This occurs very efficiently without the presence of inflammation. > NO is > known to promote it. May be other oxidants/free radical also doing > that. The increased blood flow which occurs during inflammation is not caused by oxidants - even NO plays only a minor role in this process. During inflammation a variety of chemicals are released by immune cells which increase blood flow - notably leukotrienes, compliment breakdown products, thrombin and prostiglandins. Each one of these components is 1000's of times more potent then NO in inducing vasodialation, and in addition, work over much farther distances than does NO. The vasodialtion produced by NO is considered to be predominantly something which occurs during health (i.e. its homeostatic). During infection NO appears to play two different, and somewhat conflicting roles. Firstly, many immune cells produce it, along with any other oxidants, to kill bacteria. Secondly, NO reduces the recruitment of immune cells into the region of inflammation; so rather then promoting the recruitment of immune cells it inhibits it Bryan > >>> Can there may be some relation in between oxidants/free radicals, in > >>> common, and vasodilation or muscles relaxtions whereas antioxidants [quoted text clipped - 23 lines] > they need to be continually replaced. This occurs very efficiently > without the presence of inflammation. Then, what is the purpose of increased blood flow on any inflammtion? > > NO is > > known to promote it. May be other oxidants/free radical also doing [quoted text clipped - 17 lines] > > Bryan Thanks for telling this. Can you tell reasons for these two conflicting roles? Are these conflicting roles related to acute and chronic states? >>>>> Can there may be some relation in between oxidants/free radicals, in >>>>> common, and vasodilation or muscles relaxtions whereas antioxidants [quoted text clipped - 24 lines] > > Then, what is the purpose of increased blood flow on any inflammtion? Think about it for a second, the answer is rather obvious. It takes a tremendous amount of energy to overcome and infection and repair tissue. As such, the predominant role for increased blood flow to a site of infection is to provide sufficient oxygen and nutrition for the cells in the area. A second use for the inflammation is to help induce edema (swelling, caused by the movement of serum from the blood into the tissues). Edema helps kill infections (by carrying anti-bacterial proteins from the blood into the tissues) and may also reduce the spread of infections out of the initial site of infection (by reducing flow in the lymphatics). The idea that increased blood flow was to deliver immune cells is an old one, but one which doesn't appear to be true. As I mentioned in my last post, immune cells are very efficiently recruited without increases in blood flow. Secondly, when you look at the % of immune cells which pass through an inflamed site that actually get recruited, the %age is rather small. As such, the kinds of increases in blood flow we see during inflammation would have only a minor effect on the total number of recruited immune cells. >>> NO is >>> known to promote it. May be other oxidants/free radical also doing [quoted text clipped - 19 lines] > Thanks for telling this. Can you tell reasons for these two conflicting > roles? Are these conflicting roles related to acute and chronic states? No. As I mentioned before, NO can works over very small distances (usually between cells in contact). So the differences in NO's uses are largely dictated by where the NO is being produced. So endothelial cells (which line blood vessels) that produce NO will cause vasodialation and inhibit cell recruitment. But immune cells which are outside the blood that produce NO will predominantly effect bacteria they've engulfed, and the NO they produce will not make it far enough to dramatically effect the blood vessels. Another thing worth pointing out is that these "conflicting" roles of NO actually represent an important feed-back loop. During an inflammatory reaction there are both pro- and anti-inflammatory chemicals produced. This is important for two reasons: firstly, it prevents inflammation from running out of control; and secondly, it begins to set up the chemical environment that will be required once the infection is cleared - as in the environment which promotes wound healing. Lastly, the different "conflicting" uses of NO relate more to inflamed conditions (acute or chronic inflammation) verses non-inflamed (homeostatic) conditions. Basically, under normal, non-inflamed conditions NO does it's thing without interference. It relaxes blood vessels, and helps to keep unwanted immune cells out of the uninfected tissue. But during inflammation the vaso-regulators and pro-inflammatory mediators which are produced simply overwhelm the effects of NO; and that NO is "ignored" until the levels of these other chemicals drop. Bryan > >>>>> Can there may be some relation in between oxidants/free radicals, in > >>>>> common, and vasodilation or muscles relaxtions whereas antioxidants [quoted text clipped - 97 lines] > > Bryan Thanks again. Can there be anti inflammatory conditions to the infected/diseased site to starve or deactivate disease causing agents? |
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