Talk:Endothelium-derived relaxing factor

EDRF = Nitric Oxide ?

IMHO, Nitric Oxide is an EDRF. The endothelium can release other vasorelaxing factors. Hopefully, someone would add these non-NO endothelium-derived vasorelaxing factors to this Wikipage even though they are not usually called EDRF. One example would be prostacyclin. (I might do this later....) -- PFHLai 20:36, 2004 Jun 3 (UTC)

I simply changed the wording, but the point already was that EDRF is synonymous with nitric oxide. Please expand if you think that prostacyclin (I have written eicosanoid, but not prostacyclin yet) belongs here. JFW | T@lk 23:06, 3 Jun 2004 (UTC)

It's true that EDRF is practically synonymous with Nitric Oxide (NO) even though it's not accurate -- it's like heart attack and heart failure, it will be hard to find too many people who care about the difference. NO has all the properties of EDRF as originally characterized by Furchgott, but NO is just one of the endothelial-derived compounds that acts as a vasorelaxant, i.e. an EDRF. Besides PGI2 (prostacyclin, which deserves its own Wikispace), there is carbon monoxide from heme oxygenases, but it is much, much, much weaker than NO as an EDRF. And there is also the enigmatic endothelial-derived hyperpolarizing factor, which may be short-lived compounds (I forgot their names, but I think one of them is called EET, not to be confused with ET the vasoconstrictor) generated by some P-450 cytochrome enzymes similar to cyclooxygenases .... Fun stuffs to read, but tough to fully comprehend ... (at least to my feeble mind.) Even tougher is for me to find anything in my messy office. I want to be sure of things before I start typing. If I can find those papers again, there will be additions made to this somewhat stubby Wikipage on EDRF. If I can find those papers ..... -- PFHLai 17:40, 2004 Jun 4 (UTC)

I believe EDRF should be considered synonymous with NO. When EDRF was discovered, it reflected the action of a single vasorelaxant substance with a short half-life. The actions of prostacyclin were already well known before EDRF was discovered to be NO. I don't think this article should include a description of any of the other relaxing factors. However, if you really wish to do this, the article would have to be called 'Endothelium-derived relaxing factors' (emphasis on plural), since you've already pointed out that there is more than one EDRF. In citing EDHF, you do make a good point though about whether this article should describe the other known relaxing factors. Usually vascular biologists call endothelium-derived hyperpolarizing factor to stage when they observe a relaxation that persists even under the blockade of eNOS and COX. EDHF is usually refered to as singular, even though its actions have been ascribed among others to epoxyeicosatrienoic acids (EETs), potassium ions released from endothelial cells, or even the presence of myoendothelial gap junctions. My point is that at the moment the knowledge about the precise identity of EDHF is sketchy to say the least. On the other hand EDRF is a factor that was once as impartially understood as EDHF, however all of its actions and properties could later be ascribed to NO. This cannot be said for EDHF, seeing its very heterogenous characterization. An article about EDHF should however include the many different substances and processes to which its action is ascribed. --Zorpidus 17:17, 12 Dec 2004 (UTC)

Prostacyclin (PGI2)is not characterized as an EDRF, but has been a well known prostanoid stimulating adenylate cyclase and the cAMP activating PKA before EDRF was characterized. They are both considered cyclic nucleotide-dependent vasorelaxants.GetAgrippa 18:03, 21 September 2006 (UTC)

Is heme oxygenase and carbon monoxide considered an EDRF? I agree for practical terms of this article that EDRF has become synonymous with NO. I believe at my last inquiry EDHF was related to cannibanoid like metabolites or cytochrome P450 metabolites. GetAgrippa 04:01, 7 September 2006 (UTC)

Carbon monoxide appears to interact with NO or at least activate part of the pathway of guanylate cyclase and cGMP, but cross talk to PKA activation maybe the kinase rather than PKG.GetAgrippa 18:03, 21 September 2006 (UTC)

I took out the reference to Minoxidil. It has nothing to do with EDRF and the mechanism of action in hair growth is still unknown. Minoxidil acts on ATP-sensitive potassim channels. EDRF works through altering calcium, actin-focal adhesion dynamics, and activating phosphatases just to mention the major.GetAgrippa 04:19, 7 September 2006 (UTC)

Minoxidil

"The putative nitric oxide agonist minoxidil [1] both dialates blood vessels and stimulates hair growth". This statment is ill founded so I removed it, again. Minoxidil works on ATP sensitive potasium channels. NO stimultes cGMP and then PKG. This alters L type calcium channels, calcium sensitive postassium channels, calcium pumps and phospholamban and phospholemman, calcium desensitization by altering myosin light chain phosphorylation, phosphorylation of a small heat shock protein which correlates with force suppression, etc. In fact, the small heat shock protein connection is a growing primary focus of vasodilation. I could find no peer reviewed publication connecting Minoxidil with NO, cGMP, or PKG. NO does not simply alter potassum channels as the reference would suggest. I would hope this would put this issue to rest. GetAgrippa 16:15, 21 September 2006 (UTC)

Well this minoxidil thing bothers me because it is a nitroso compound, so it may act similar to nitrates. However I still can't find any research to substantiate any NO like effects and it seems specific to ATP sensitive potassium channels. That is why it won't relax vascular smooth muscle strips contracted with high potassium, while NO will relax these conditions. GetAgrippa 00:40, 22 September 2006 (UTC)

Minoxidel does not increase cGMP or cAMP and it's vasodilatory effects are specific to potassium channel and apparently direct.GetAgrippa 00:46, 22 September 2006 (UTC)

NO also modulates the action of K channels. LOTS of papers (do K-channels and nitric oxide as key words on google). E.g.: [2]. In fact, this may be more important than action on guanylate cyclase.24.162.6.155 03:56, 14 December 2006 (UTC)

My understanding is PKA and PKG stimulate hyperpolarization via potassium channels so it is downstream of NO. I forgot to add a mention in general list, but I referenced smooth muscle article that goes into more detail of NO action. GetAgrippa 12:10, 14 December 2006 (UTC)

This is one likely mechanism, but probably not the only one. IIRC, there are direct actions of NO on K-channels too. As for miNOxidil, other issues aside, when I took pharmacology over three decades ago (my PhD says Pharmacology/biophysics), if a compound contained a messenger as part of its chemical structure and did the same thing at a "receptor site" as the messenger, and/or had the same effect on a tissue (e.g., direct vascular smooth muscle relaxation) it was likely an agonist of some sort. And yes, there are different types of agonism. In fact, "pure" agonism or antagonism is unusual. YMMV, naturally.

This does not necessarily mean the active form is miNOxidil itself. e.g., the sulfate or some derivative. E.g., the minoxidil nitroxide radical thru the sulfate, though this is definitely OR. So I ain't going to say it on the article page. Also, there is other "classical' evidence from agonist-antagoist relationships. E.g., SOD's stimulate hair growth-- viz, the agonist/antagonist relationship between NO and superoxide. Another name for superoxide is "endothelium-derived-contracting factor. Nicorandil, another "nitro" compound which acts on K-channels, is also a hair-growth stimulator. Pproctor 15:26, 14 December 2006 (UTC)

Wow, I was unaware of the Potassium hypothesis in hair growth. A number of drugs affecting potassium flux induce hair growth. I agree that cGMP and NO itself have some direct actions (or at least react to produce agents that induce vasorelaxant and/or contractile responses). The importance of hyperpolarization in vascular relaxation is somewhat dependent on the vessel-hyperpolarization significant in resistance vessels (PKA mediated). My Ph.D. was in cell biology and anatomy but most of my research has been in cardiovascular developmental biology, physiology, biomechanics, and more recently cell signalling, however I published a couple of papers in neuro and five or so in immunology. It is wonderful to have a "card carrying" pharmacologist to cleanup this article. Perhaps you could sound out the distinctions between endothelial hyperpolarizing factor from other agents that affect varying potassium channels,i.e. physiochemical distinctions, antagonist, etc. The article needs a lot of work, and the subject has received little attention. Perhaps you could help develop the article? GetAgrippa 16:40, 14 December 2006 (UTC)

I see you have done significant research in hair growth and mainly have an interest in free radicals. It would be a great subject to expand. My last research efforts were in vasorelaxation cell signalling and downstream mediators of NO (mainly PKA and PKG phosphosubtrates looking for novel proteins and mechanisms). GetAgrippa 17:00, 14 December 2006 (UTC)

Viagra

I removed the reference to sildenafil (Viagra). It is a type 5 phosphodiesterase inhibitor and increase cGMP. It is not related to NO. GetAgrippa 12:57, 26 September 2006 (UTC)

Viagra should be added back in since although it does not act through NO it does act through the same pathway as NO to relax smooth muscle and promote erection. GetAgrippa has edited Viagra out but what s/he describes IS the pathway of NO. It acts through cGMP just like s/he describes viagra doing. Please refer to the mechanism of action section of Viagra

Guanylin also activates the cGMP-PKG pathway. It is not enough to have a related pathway in cell signalling so I still think the distinction should be made. It is also discussed later in the article so it is redundant. GetAgrippa 20:04, 10 December 2006 (UTC)

"Biological functions of nitric oxide"

I would prefer to move this article to "Biological functions of nitric oxide" because some functions described here don't have anything to do with the endothelium and relaxing, namely its function in the immune system and as a reverse neurotransmitter. Then we could also list its functions in the plant kingdom, which are closely related and surprisingly similar (e.g. Viagra works on plants!). The fact that the relaxing substance was called EDRF before its chemical identity had been descovered could and should be mentioned in that article. AxelBoldt 00:20, 11 February 2007 (UTC)

There is a nitric oxide article and I think all the biology was removed and place here, at least at one time it was. You are correct we should just focus on endothelial source and functions. GetAgrippa 12:25, 12 February 2007 (UTC)

Well, I wasn't saying we should just focus on endothelial source and function, actually just the opposite: the functions in plants are so closely related that they should be covered as well, but clearly the functions in plants don't belong under the article header "endothelium-derived"... AxelBoldt 06:35, 13 February 2007 (UTC)

The United States National Library of Medicine stopped equating EDRF with NO in 2003. --Arcadian 17:46, 18 February 2007 (UTC)

That is a really good point. EDRF's are more than one compound and they had to be sorted to physiochemical properties, so the most famous EDRF latter became known as NO. I think endothelial hyperpolarization factor was initially classified as an EDRF and sorted out with time. Perhaps a historical note should be made or this be a sort of disambiguation page. Now it is NO so why go back in time. Maybe we should just suggest fusing this article with NO and expanding all the NO sources there. Any ideas??GetAgrippa 18:30, 22 September 2007 (UTC)

Well I decided to be bold and tweak the intro to explain the EDRF was factors sorted out to be NO, etc. I don't know if Heme oxygenase should really be in here because it is induced in the endothelium and is constituitively expressed in smooth muscle. Any insights????GetAgrippa 18:58, 22 September 2007 (UTC)

Now I have created the need to expand and either include PGI2, EDHF, and HO-1 (hsp 32) or link them if the article is present. They all have parent articles so we are covered. User:GetAgrippa|GetAgrippa]] 19:03, 22 September 2007 (UTC)

Article Butchered by Naive Editor

This article has been drastically changed without discussion. The article has been in dire need, and this edit has drastically simplified the article. This is probably good, but now the article needs to be expanded. GetAgrippa (talk) 23:11, 15 December 2007 (UTC)