Abstract
Arterial hypertension is a worldwide public health threat. High Blood Pressure (BP) is commonly associated with endothelial dysfunction, nitric oxide synthases (NOS) unbalance and high peripheral vascular resistance. In addition to those, inflammation has also been designated as one of the major components of BP increase and organ damage in hypertension. This minireview discusses vascular inflammatory triggers of high BP and aims to fill the existing gaps of antiinflammatory therapy of hypertension. Among the reasons discussed, enhanced prostaglandins rather than resolvins lipid mediators, immune cell infiltration and oxidative/nitrosative stress are pivotal players of BP increase within the inflammatory hypothesis. To address these inflammatory targets, this review also proposes new concepts in hypertension treatment with non-steroidal antiinflammatory drugs (NSAIDs), nitric oxide-releasing NSAIDs (NO-NSAIDs) and specialized proresolving mediators (SPM). In this context, the failure of NSAIDs in hypertension treatment seems to be associated with the reduction of endogenous NO bioavailability, which is not necessarily an effect of all drug members of this pharmacological class. For this reason, NO-releasing NSAIDs seem to be safer and more specific therapy to treat vascular inflammation in hypertension than regular NSAIDs.
Keywords: Hypertension, vascular inflammation, cyclooxygenases, NF-κB, iNOS, NSAIDs, NO-NSAIDs.
Graphical Abstract
[http://dx.doi.org/10.1016/j.jash.2012.11.007] [PMID: 23321405]
[http://dx.doi.org/10.1111/bph.14436] [PMID: 29969833]
[http://dx.doi.org/10.1038/nature07201] [PMID: 18650913]
[http://dx.doi.org/10.1016/j.maturitas.2014.04.012] [PMID: 24846805]
[http://dx.doi.org/10.1155/2019/3159283] [PMID: 31186952]
[http://dx.doi.org/10.1016/j.phrs.2017.02.026] [PMID: 28279813]
[http://dx.doi.org/10.1161/JAHA.115.002073] [PMID: 26391131]
[http://dx.doi.org/10.1038/s41440-019-0245-3] [PMID: 30850753]
[http://dx.doi.org/10.1080/10641963.2018.1510942] [PMID: 30183451]
[http://dx.doi.org/10.1080/10641960500298673] [PMID: 16303639]
[PMID: 31516762]
[http://dx.doi.org/10.1111/j.1440-1681.2010.05394.x] [PMID: 20456428]
[http://dx.doi.org/10.1002/acr.23171] [PMID: 27998029]
[http://dx.doi.org/10.1016/j.ijcard.2018.06.111] [PMID: 30007486]
[http://dx.doi.org/10.1161/JAHA.116.005394] [PMID: 28242635]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.04006] [PMID: 25024282]
[http://dx.doi.org/10.1038/jhh.2013.80] [PMID: 24005958]
[http://dx.doi.org/10.1093/rheumatology/kez114] [PMID: 31329965]
[http://dx.doi.org/10.1161/CIRCRESAHA.116.303697] [PMID: 25767287]
[http://dx.doi.org/10.1016/j.molcel.2017.05.009] [PMID: 28622520]
[http://dx.doi.org/10.1007/s11357-012-9402-1] [PMID: 22453933]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.111.034470] [PMID: 21875910]
[http://dx.doi.org/10.1042/CS20110523] [PMID: 22233532]
[http://dx.doi.org/10.1093/cvr/cvv137] [PMID: 25910936]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.024369] [PMID: 27803035]
[http://dx.doi.org/10.1093/eurheartj/ehu119] [PMID: 24685711]
[http://dx.doi.org/10.1084/jem.20070657] [PMID: 17875676]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.115.05779] [PMID: 26351030]
[http://dx.doi.org/10.1007/s11906-019-0907-1] [PMID: 30659373]
[http://dx.doi.org/10.1126/scitranslmed.aah4923] [PMID: 28148841]
[http://dx.doi.org/10.2174/1573402113666170413095508] [PMID: 28412915]
[http://dx.doi.org/10.1016/j.carpath.2015.07.007] [PMID: 26365806]
[http://dx.doi.org/10.1016/j.bbadis.2014.07.008] [PMID: 25045854]
[http://dx.doi.org/10.1152/ajplung.00389.2003] [PMID: 15090367]
[http://dx.doi.org/10.1161/01.RES.0000237388.89261.47] [PMID: 16857964]
[http://dx.doi.org/10.1186/1423-0127-21-3] [PMID: 24410814]
[http://dx.doi.org/10.1093/cvr/cvy023] [PMID: 29394331]
[http://dx.doi.org/10.1038/hr.2017.72] [PMID: 28878301]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.00995] [PMID: 23734008]
[http://dx.doi.org/10.1111/bph.13457] [PMID: 26856544]
[http://dx.doi.org/10.1161/01.HYP.0000253085.56217.11] [PMID: 17145980]
[http://dx.doi.org/10.3389/fimmu.2018.02739] [PMID: 30538702]
[http://dx.doi.org/10.3390/antiox8060193] [PMID: 31234522]
[http://dx.doi.org/10.1038/sj.bjp.0707190] [PMID: 17351662]
[http://dx.doi.org/10.1111/j.1476-5381.2008.00060.x] [PMID: 19154435]
[http://dx.doi.org/10.1016/j.mcna.2016.08.004] [PMID: 27884227]
[http://dx.doi.org/10.1038/sj.bjp.0707575] [PMID: 17994107]
[http://dx.doi.org/10.1111/j.1476-5381.2011.01360.x] [PMID: 21434884]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.178129] [PMID: 21931069]
[http://dx.doi.org/10.2174/13894501113146660227] [PMID: 24102471]
[http://dx.doi.org/10.3109/10715762.2012.731052] [PMID: 22998079]
[http://dx.doi.org/10.1152/ajpregu.00355.2012] [PMID: 23389111]
[http://dx.doi.org/10.2174/0929867323666160729105312] [PMID: 27480213]
[http://dx.doi.org/10.1016/j.bcp.2008.11.004] [PMID: 19046943]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.189407] [PMID: 22252393]
[http://dx.doi.org/10.1016/j.phrs.2019.04.029] [PMID: 31039397]
[http://dx.doi.org/10.3389/fphar.2018.01488] [PMID: 30618774]
[http://dx.doi.org/10.1161/CIRCRESAHA.116.307308] [PMID: 27340271]
[http://dx.doi.org/10.1096/fj.14-265363] [PMID: 25777995]
[http://dx.doi.org/10.1111/bph.14151] [PMID: 29352769]
[http://dx.doi.org/10.1097/HJH.0000000000001143] [PMID: 27906841]
[http://dx.doi.org/10.1371/journal.pone.0142848] [PMID: 26565966]
[http://dx.doi.org/10.1161/ATVBAHA.118.311296] [PMID: 30571171]
[http://dx.doi.org/10.1152/ajpheart.00748.2007] [PMID: 17766473]
[http://dx.doi.org/10.1001/archinte.1993.00410040045007] [PMID: 8435027]
[http://dx.doi.org/10.1111/j.1476-5381.2009.00611.x] [PMID: 20128814]
[http://dx.doi.org/10.1161/CIRCOUTCOMES.108.805689] [PMID: 20031832]
[http://dx.doi.org/10.1111/jcpt.12484] [PMID: 28019014]
[http://dx.doi.org/10.1186/1471-2261-12-93] [PMID: 23092442]
[http://dx.doi.org/10.1080/00325481.2018.1412799] [PMID: 29202670]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.05105] [PMID: 26169048]
[http://dx.doi.org/10.1016/j.amjmed.2011.02.025] [PMID: 21596367]
[http://dx.doi.org/10.1111/bph.14167] [PMID: 29468666]
[http://dx.doi.org/10.3390/ijms20174262] [PMID: 31480335]
[http://dx.doi.org/10.1073/pnas.1209192109] [PMID: 23045674]
[http://dx.doi.org/10.3109/10641963.2013.776567] [PMID: 23489008]
[http://dx.doi.org/10.1139/Y10-112] [PMID: 21326341]
[http://dx.doi.org/10.3389/fphys.2017.00138] [PMID: 28344559]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.114.011591] [PMID: 25492024]
[http://dx.doi.org/10.1042/CS20030412] [PMID: 15182236]
[http://dx.doi.org/10.1248/cpb.60.465] [PMID: 22466730]
[http://dx.doi.org/10.1016/S0024-3205(98)00072-1] [PMID: 9566780]
[http://dx.doi.org/10.1152/ajpheart.2000.279.2.H528] [PMID: 10924050]
[http://dx.doi.org/10.1016/j.phrs.2013.09.008] [PMID: 24083950]
[http://dx.doi.org/10.1016/j.ejps.2017.06.007] [PMID: 28603034]
[http://dx.doi.org/10.1002/art.27694] [PMID: 20722026]
[http://dx.doi.org/10.1111/j.1751-7176.2010.00419.x] [PMID: 21545399]
[http://dx.doi.org/10.1155/2016/8128957] [PMID: 27642495]
[PMID: 29375050]
[http://dx.doi.org/10.2174/1568014043355294]
[http://dx.doi.org/10.1038/sj.bjp.0703603] [PMID: 11015317]
[http://dx.doi.org/10.1016/j.amjhyper.2006.12.003] [PMID: 17531919]
[http://dx.doi.org/10.1080/10641963.2016.1210628] [PMID: 28055264]
[http://dx.doi.org/10.1152/ajpheart.00548.2003] [PMID: 15001439]
[http://dx.doi.org/10.1038/aps.2010.111] [PMID: 20835265]
[http://dx.doi.org/10.1111/micc.12382] [PMID: 28510986]
[http://dx.doi.org/10.1124/jpet.105.088062] [PMID: 15951402]
[http://dx.doi.org/10.1016/j.taap.2015.02.023] [PMID: 25759242]
[PMID: 25816715]
[http://dx.doi.org/10.1007/s12012-015-9344-9] [PMID: 26438340]
[http://dx.doi.org/10.3181/00379727-221-44381] [PMID: 10320629]
[http://dx.doi.org/10.1152/ajpheart.00823.2014] [PMID: 25910811]
[http://dx.doi.org/10.3390/molecules19033247] [PMID: 24642910]
[http://dx.doi.org/10.1016/j.ejphar.2016.11.040] [PMID: 27890711]
[http://dx.doi.org/10.4049/jimmunol.1201272] [PMID: 22844113]
[http://dx.doi.org/10.1093/eurheartj/ehx508] [PMID: 29020251]
[http://dx.doi.org/10.1097/HJH.0b013e328325d831] [PMID: 19516186]
[PMID: 27981528]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.04980] [PMID: 25691622]
[http://dx.doi.org/10.1097/HJH.0b013e3283310dc9] [PMID: 19887957]
[http://dx.doi.org/10.1016/j.joca.2009.12.013] [PMID: 20202489]
[http://dx.doi.org/10.1016/j.amjcard.2009.05.014] [PMID: 19733721]
[http://dx.doi.org/10.1016/j.semarthrit.2010.06.002] [PMID: 20828790]