Target Organ Damage in Hypertension: Pathophysiology and Implications for Drug Therapy

Nadar, Sunil; Tayebjee, Muzahir H.; Messerli, Franz H.; Lip, Gregory Y.H.

doi:10.2174/138161206776843368

Cited by 70 publications

(42 citation statements)

References 143 publications

(160 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1 Endothelial cell injury initiates adhesion molecule and chemokine expression promoting inflammation that contributes to the pathogenesis of hypertension-induced target organ damage. [2][3][4][5] Patients with severe hypertension and target-organ damage often show elevated angiotensin (Ang) II levels and reduced nitric oxide (NO) production.…”

mentioning

confidence: 99%

Vascular Endothelial Cell–Specific NF-κB Suppression Attenuates Hypertension-Induced Renal Damage

Henke

Schmidt‐Ullrich

Dechend

et al. 2007

Circulation Research

129

View full text Add to dashboard Cite

Abstract-Nuclear factor kappa B (NF-B) participates in hypertension-induced vascular and target-organ damage. We tested whether or not endothelial cell-specific NF-B suppression would be ameliorative. We generated Cre/lox transgenic mice with endothelial cell-restricted NF-B super-repressor IB␣⌬N (Tie-1-⌬N mice) overexpression. We confirmed cell-specific IB␣⌬N expression and reduced NF-B activity after TNF-␣ stimulation in primary endothelial cell culture. To induce hypertension with target-organ damage, we fed mice a high-salt diet and N(omega)-nitro-Larginine-methyl-ester (L-NAME) and infused angiotensin (Ang) II. This treatment caused a 40-mm Hg blood pressure increase in both Tie-1-⌬N and control mice. In contrast to control mice, Tie-1-⌬N mice developed a milder renal injury, reduced inflammation, and less albuminuria. RT-PCR showed significantly reduced expression of the NF-B targets VCAM-1 and ICAM-1, compared with control mice. Thus, the data demonstrate a causal link between endothelial NF-B activation and hypertension-induced renal damage. We conclude that in vivo NF-B suppression in endothelial cells stops a signaling cascade leading to reduced hypertension-induced renal damage despite high blood pressure. Key Words: hypertension Ⅲ endothelium Ⅲ NF-B Ⅲ target-organ damage H ypertension is a risk factor for target-organ damage such as cardiac and renal disease. 1 Endothelial cell injury initiates adhesion molecule and chemokine expression promoting inflammation that contributes to the pathogenesis of hypertension-induced target organ damage. [2][3][4][5] Patients with severe hypertension and target-organ damage often show elevated angiotensin (Ang) II levels and reduced nitric oxide (NO) production. Ang II signaling blockade reduces blood pressure and blunts the development and progression of vascular disease in small and large vessels in experimental animal models and in humans. Ang II also elicits an inflammatory response in both endothelial cells 6 and vascular smooth muscle cells. 7,8 Numerous in vitro and in vivo studies demonstrated that Ang II activates the nuclear factor kappa B (NF-B), a major transcription factor in mediating inflammation and innate immunity. 4,6 -8 In resting cells, NF-B resides inactive in the cytoplasm by forming complexes with the inhibitor of B (I〉) proteins. Exposure to extracellular stimuli like TNF-␣, IL-1, reactive oxygen species, Ang II, and numerous other activators leads to rapid phosphorylation, site-specific ubiquitination, and subsequent degradation of the IB proteins by the 26S proteasome. 9 The resulting free NF-B molecules translocate to the nucleus and regulate target gene expression. The targets include genes involved in the control of cell proliferation, apoptosis, innate, and adaptive immune response. 10,11 NF-B and inflammation play an important role in the development of the target organ damage. 4,[12][13][14][15][16][17] However, inhibition of NF-B signaling could also be detrimental. 18,19 Furthermore, the ideal site for NF-B inhibition in the vesse...

show abstract

mentioning

confidence: 99%

Vascular Endothelial Cell–Specific NF-κB Suppression Attenuates Hypertension-Induced Renal Damage

Henke

Schmidt‐Ullrich

Dechend

et al. 2007

Circulation Research

129

View full text Add to dashboard Cite

show abstract

“…[20][21][22] The goal of therapy in hypertensive patients with an acute coronary syndrome is to minimize ischemia. In patients with a history of mild or no hypertension, vasodilator therapy can be titrated for symptom …”

Section: Cardiovascular Hypertensive Emergenciesmentioning

confidence: 99%

When Is Hypertension a True Crisis and How Should It Be Managed in the Intensive Care Unit?

Augoustides¹

2010

Evidence-Based Practice of Critical Care

View full text Add to dashboard Cite

“…TOD is the structural and functional impairment of major body organs due to elevated blood pressure (BP). These vital organ impairments including left ventricular hypertrophy (LVH), proteinuria, retinopathy, and vascular dementia are collectively referred as target organ damage [5]. The heart, brain, and kidney are the main target of elevated blood pressure because these organs take the large share of the blood circulating in the vasculature [6].…”

Section: Introductionmentioning

confidence: 99%

Target Organ Damage And The Long Term Effect of Nonadherence To Clinical Practice Guidelines In Patients With Hypertension: A Retrospective Cohort Study

2017

View full text Add to dashboard Cite

Background. There was limited published data on target organ damage (TOD) and the effect of nonadherence to practice guidelines in Ethiopia. This study determined TOD and the long term effect of nonadherence to clinical guidelines on hypertensive patients.Methods. An open level retrospective cohort study has been employed at cardiac clinic of Gondar university hospital for a mean follow-up period of 78 months. Multivariate Cox regression was conducted to test associating factors of TOD. Results. Of the total number of 612 patients examined, the overall prevalence of hypertensive TOD was 40.3%. The presence of comorbidities, COR = 1.073 [1.01-1.437], AOR = 1.196 [1.174-1.637], and nonadherence to clinical practice guidelines, COR = 1.537 [1.167-2.024], AOR = 1.636 [1.189-2.251], were found to be predicting factors for TOD. According to Kaplan-Meier analysis patients who were initiated on appropriate medication tended to develop TOD very late: Log Rank [11.975 ( = 0.01)]. Conclusion. More than forty percent of patients acquired TOD which is more significant. Presence of comorbidities and nonadherence to practice guidelines were correlated with the incidence of TOD. Appropriate management of hypertension and modification of triggering factors are essential to prevent complications.

show abstract

Target Organ Damage in Hypertension: Pathophysiology and Implications for Drug Therapy

Cited by 70 publications

References 143 publications

Vascular Endothelial Cell–Specific NF-κB Suppression Attenuates Hypertension-Induced Renal Damage

Vascular Endothelial Cell–Specific NF-κB Suppression Attenuates Hypertension-Induced Renal Damage

When Is Hypertension a True Crisis and How Should It Be Managed in the Intensive Care Unit?

Target Organ Damage And The Long Term Effect of Nonadherence To Clinical Practice Guidelines In Patients With Hypertension: A Retrospective Cohort Study

Contact Info

Product

Resources

About