Angiotensin-Converting Enzyme Inhibitors

Peng, Hongmei; Carretero, Oscar A.; Vuljaj, Nikola; Liao, Tang Dong; Motivala, Apurva; Peterson, Edward L.; Rhaleb, Nour Eddine

doi:10.1161/circulationaha.104.528695

Cited by 141 publications

(135 citation statements)

References 47 publications

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“…In animal models of pressure overloadinduced LV hypertrophy, a transient increase in cytokine release and macrophage infiltration 28 has been shown, and Hsieh et al 29 have demonstrated that NOS inhibition with L-NAME in hypertensive rats increases vascular inflammation. Although previous studies have demonstrated that ACE inhibitor treatment reduces macrophage infiltration and cellular proliferation following myocardial infarction, 30 the present study is the first to demonstrate that these beneficial effects persist well after stopping treatment. Specifically, there was a 450% reduction in the number of macrophages in the LV of SHR previously treated with enalapril.…”

Section: Discussioncontrasting

confidence: 45%

Short-term ACE inhibition confers long-term protection against target organ damage

et al. 2012

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Angiotensin converting enzyme (ACE) inhibitors reduce left ventricular (LV) hypertrophy and cardiovascular-renal fibrosis. Experimentally, changes in the LV and kidney persist even after cessation of treatment. The present study investigates whether brief ACE inhibition in spontaneously hypertensive rats (SHR) provides long-term protection against the LV and kidney damage induced by the nitric oxide synthase inhibitor N-x-nitro-L-arginine-methyl ester (L-NAME). SHR received the ACE inhibitor enalapril (n¼36) or tap water (n¼36). In all, 12 control and treated SHR were sacrificed after 2 weeks and remaining rats were taken off-treatment. After a 2-week washout, 12 controls or previously treated SHR were sacrificed and remaining rats were treated with L-NAME ((control (Con)+L, enalapril (Enal)+L) for 10 days. At sacrifice, blood pressure was recorded via carotid artery cannulation in anesthetized rats, and blood, the kidney and LV were isolated for analysis. LV mass and arterial pressure were significantly reduced by enalapril. LV mass showed a persistent reduction throughout the study. In LV, prior enalapril treatment provided significant (Po0.05) protection against L-NAME-induced increases in proliferating cells (Con+L: 11±10.0 mm 2 vs. Enal+L: 4±4.4 mm 2 ), interstitial fibrosis (Con+L: 3±2.5% vs. Enal+L: 1±1.0%) and tissue macrophages (Con+L: 12±9 mm 2 vs. Enal+L: 5±3.6 mm 2 ). In the kidney, prior enalapril treatment protected against L-NAME-induced interstitial fibrosis and vascular injury. There was no difference in glomerular size or glomerulosclerosis regardless of prior treatment. Plasma creatinine and urea were significantly increased in L-NAME treated rats. This study suggests that brief ACE inhibition confers protection against future heart and kidney injury, even in the absence of continued antihypertensive treatment.

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Section: Discussioncontrasting

confidence: 45%

Short-term ACE inhibition confers long-term protection against target organ damage

et al. 2012

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“…Morrissey et al (25) showed that ACE inhibitors suppressed NF-κB activation, MCP-1 expression and macrophage infiltration in a UUO rat model. Ac-SDKP, a ubiquitous tetrapeptide hydrolyzed almost exclusively by the angiotensin-converting enzyme, has been shown to have similar anti-inflammatory effects as angiotensin-converting enzyme inhibitors (26,27). In the present study, Ac-SDKP markedly decreased the activation of NF-κB in the UUO/vehicle group kidneys as shown by immunohistochemical staining.…”

Section: Discussionsupporting

confidence: 63%

N-acetyl-seryl-aspartyl-lysyl-proline attenuates renal inflammation and tubulointerstitial fibrosis in rats

Wang

Liu²,

Jia³

et al. 2010

Int J Mol Med

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Abstract. It has been reported that N-acetyl-seryl-aspartyllysyl-proline (Ac-SDKP) attenuates renal and cardiac inflammation as well as fibrosis in hypertensive rats. In this study, we investigated these effects using a unilateral ureteral obstruction (UUO) model. Eighteen male Wistar rats were randomly divided into three groups: control, UUO/vehicle and UUO/Ac-SDKP groups. Animal models of renal inflammation and tubulointerstitial fibrosis were established with unilateral ureteral ligation in rats. Ac-SDKP and vehicle were infused subcutaneously by using osmotic mini pumps for two weeks. On the 14th day post-injection, kidney histological changes of each group were observed by hematoxylin-eosin and Masson's stain. Renal macrophage infiltration, together with protein expression and localization of monocyte chemoattractant protein-1 (MCP-1), nuclear factor-kappa B (NF-κB), ·-smooth muscle actin (·-SMA) and transforming growth factor-ß1 (TGF-ß1) in renal tissue was assessed by immunohistochemical staining. Gene expression of MCP-1 and TGF-ß1 was analyzed with reverse transcription-polymerase chain reaction. Ac-SDKP-treated animals demonstrated less severe renal inflammation and tubulointerstitial fibrosis. Interstitial fibrosis was significantly attenuated with Ac-SDKP. ED-1 was expressed in the interstitium of the UUO/vehicle group kidneys and decreased with Ac-SDKP treatment. MCP-1, NF-κB, ·-SMA and TGF-ß1 were increased in the renal interstitium and tubular epithelial cells of the UUO/vehicle group. Ac-SDKP significantly reduced their expressions. Gene expressions of MCP-1 and TGF-ß1 were upregulated in the UUO/vehicle group kidneys and were significantly inhibited by Ac-SDKP. In conclusion, in the rat UUO model Ac-SDKP administration protected against renal inflammation and tubulointerstitial fibrosis. The inhibitory effect of Ac-SDKP was mediated by the reduction in the expression of MCP-1, NF-κB, ·-SMA and TGF-ß1.

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“…ACE inhibitors have multiple entry points to affect the renin-angiotensin (40,41,45) and the kallikrein-kinin systems (6,(13)(14)(15)(30)(31)(32)(33)(46)(47)(48)(49)(50). Besides inhibiting the hydrolysis of ACE substrates, complex formation between ACE and the bradykinin receptors may contribute to the potentiation of B 2 receptor agonists by ACE inhibitors, (15,51) and some endogenous peptides (19).…”

Section: Discussionmentioning

confidence: 99%

Human ACE and bradykinin B ₂ receptors form a complex at the plasma membrane

et al. 2006

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To investigate how angiotensin-I converting enzyme (ACE) inhibitors enhance the actions of bradykinin (BK) on B 2 receptors independent of blocking BK inactivation, we expressed human somatic ACE and B 2 receptors in CHO cells. Bradykinin and its ACE-resistant analogue were the receptor agonists. B 2 fused with green fluorescent protein (GFP) and ACE were coprecipitated with antisera to GFP or ACE shown in Western blots. Immunohistochemistry of fixed cells localized ACE by red color and B 2 -GFP by green. Yellow color on plasma membranes of coexpressing cells also indicated enzyme-receptor complex formation. Using ACE-fused cyan fluorescent protein donor and B 2 -fused yellow fluorescent protein acceptor, we registered fluorescence resonance energy transfer (FRET) by the enhanced fluorescence of donor upon acceptor photo-bleaching, establishing close (within 10 nm) positions of B 2 receptors and ACE. Bradykinin stimulation cointernalized ACE and B 2 receptors. We expressed ACE fused to N-terminus of B 2 receptors, anchoring only receptors to plasma membranes. Here, in contrast to cells where both ACE and B 2 receptors are separately anchored, ACE inhibitors neither enhance activation of chimeric B 2 , nor resensitize desensitized B 2 receptors. Heterodimer formation between ACE and B 2 receptors can be a mechanism for ACE inhibitors to augment kinin activity at cellular level.

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Angiotensin-Converting Enzyme Inhibitors

Cited by 141 publications

References 47 publications

Short-term ACE inhibition confers long-term protection against target organ damage

Short-term ACE inhibition confers long-term protection against target organ damage

N-acetyl-seryl-aspartyl-lysyl-proline attenuates renal inflammation and tubulointerstitial fibrosis in rats

Human ACE and bradykinin B ₂ receptors form a complex at the plasma membrane

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Angiotensin-Converting Enzyme Inhibitors

Cited by 141 publications

References 47 publications

Short-term ACE inhibition confers long-term protection against target organ damage

Short-term ACE inhibition confers long-term protection against target organ damage

N-acetyl-seryl-aspartyl-lysyl-proline attenuates renal inflammation and tubulointerstitial fibrosis in rats

Human ACE and bradykinin B 2 receptors form a complex at the plasma membrane

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Human ACE and bradykinin B ₂ receptors form a complex at the plasma membrane