Published online before print October 6, 2008, doi: 10.1161/HYPERTENSIONAHA.108.121376
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(Hypertension. 2008;52:e136.)
© 2008 American Heart Association, Inc.
Letters to the Editor |
Response to Inflammation, Angiotensin II, and Hypertension
Hypertension and Vascular Research ER 7, Henry Ford Hospital, Detroit, Mich
PDL BioPharma, Inc, Fremont, Calif
Hypertension and Vascular Research ER 7, Henry Ford Hospital, Detroit, Mich
The hypothesis that inflammation plays a role in the pathogenesis of hypertension is supported by epidemiological studies indicating that inflammatory markers are associated with hypertension.1,2 However, association does not necessarily indicate cause and effect. Evidence that inflammation may participate in the pathogenesis of various models of experimental hypertension is provided by the use of immunosuppressive drugs. As indicated in the letter by Rodriguez-Iturbe et al,3 these compounds prevent inflammatory cell infiltration and decrease blood pressure. There are many other anti-inflammatory drugs, such as nonsteroidal anti-inflammatory agents or glucocorticoids, that do not ameliorate hypertension. On the contrary, they tend to antagonize the effect of antihypertensive agents and in some cases cause and aggravate hypertension. The explanation for the hypertensive effect of these drugs is that their adverse effects cause an increase in blood pressure. Drugs with immunosuppressive properties that decrease blood pressure, such as mycophenolate mofetil, an inhibitor of inosine monophosphate dehydrogenase, that inhibits de novo purine synthesis; pyrrolidine dithiocarbamate, an inhibitor of nuclear factor 
B; or cyclophosphamide, a nitrogen mustard alkylating agent, also have multiple adverse effects, such as inhibition of cell proliferation, diarrhea, nausea, fatigue, loss of body weight, etc, which may cause a decrease in blood pressure. Many of these drugs are not only used to treat autoimmune disorders but also various types of cancer. To attribute their effect on blood pressure to the decreased inflammatory response is not well justified. We have recently used a naturally occurring peptide in mammals with anti-inflammatory properties, N-acetyl-seryl-aspartyl-lysyl-proline; this peptide decreases inflammation and fibrosis, but it does not change blood pressure in various models of hypertension, including mineralocorticoids-salt-induced hypertension.4 Another approach to study the role of inflammation in the pathogenesis of hypertension is the use of genetically modified mice. In an article in Hypertension,5 we used mice lacking the CC chemokine receptor 2. In these mice, angiotensin II caused increases in blood pressure similar to those in wild-type mice; however, inflammation in the kidney was significantly decreased.5 Rodriguez-Iturbe et al3 argue that the reason that the blood pressure did not decrease was that we infused a pharmacological dose of angiotensin II. This may be the case; however, one should take into consideration that mice require a higher amount of angiotensin II to induce hypertension. The dose used by our group is similar to that used by their group (520 ng/kg per minute versus 435 ng/kg per minute). Their model is different in that the angiotensin II was stopped before the rats were placed on a high-sodium diet. It could be that, in their model of salt-sensitive hypertension, inflammation is more relevant in the development of high blood pressure. Nevertheless, this model of hypertension needs to be confirmed by an independent group of investigators. In addition to the mice lacking the CC chemokine receptor 2, other models of genetically modified mice with altered immune response have yielded both positive and negative results.6,7 Thus, at the present time, whether inflammation participates in the pathogenesis of hypertension remains an open question.
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Acknowledgments |
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Source of Funding
Funding provided by NIH grant HL-028982.
Disclosures
None.
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References |
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 Top References |
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1. Bautista LE, López-Jaramillo P, Vera LM, Casas JP, Otero AP, Guaracao AI. Is C-reactive protein an independent risk factor for essential hypertension? J Hypertens. 2001; 19: 857–861.[CrossRef][Medline] [Order article via Infotrieve]
2. Bautista LE. Inflammation, endothelial dysfunction, and the risk of high blood pressure: epidemiologic and biological evidence. J Hum Hypertens. 2003; 17: 223–230.[CrossRef][Medline] [Order article via Infotrieve]
3. Rodriguez-Iturbe B, Vaziri ND, Johnson RJ. Inflammation, angiotensin II, and hypertension. Hypertension. 2008; 52: e135.
4. Peng H, Carretero OA, Raij L, Yang F, Kapke A, Rhaleb N-E. Antifibrotic effects of N-acetyl-seryl-aspartyl-lysyl-proline on the heart and kidney in aldosterone-salt hypertensive rats. Hypertension. 2001; 37: 794–800.
5. Liao T-D, Yang X-P, Liu Y-H, Shesely EG, Cavasin MA, Kuziel WA, Pagano PJ, Carretero OA. Role of inflammation in the development of renal damage and dysfunction in angiotensin-II-induced hypertension. Hypertension. 2008; 52: 256–263.
6. Lee DL, Sturgis LC, Labazi H, Osborne JB Jr, Fleming C, Pollock JS, Manhiani M, Imig JD, Brands MW. Angiotensin II hypertension is attenuated in interleukin-6 knockout mice. Am J Physiol Heart Circ Physiol. 2006; 290: H935–H940.
7. Raij L, Dalmasso AP, Staley NA, Fish AJ. Renal injury in DOCA-salt hypertensive C5-sufficient and C5-deficient mice. Kidney Int. 1989; 36: 582–592.[Medline] [Order article via Infotrieve]
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