The protective effect of angiotensin converting enzyme inhibition in experimental renal fibrosis in mice is not mediated by bradykinin B2 receptor activation

2003 ◽  
Vol 89 (04) ◽  
pp. 735-740 ◽  
Author(s):  
Joost Schanstra ◽  
Johan Duchene ◽  
Laurence Desmond ◽  
Eric Neau ◽  
Denis Calise ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renal Fibrosis ◽  
Ace Inhibition ◽  
Receptor Activation ◽  
Tubulointerstitial Fibrosis ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
Bradykinin B2 Receptor ◽  
Renal Tubulointerstitial Fibrosis ◽  
At1 Receptor Antagonists

SummaryUnilateral ureteral obstruction (UUO) is an animal model of accelerated renal tubulointerstitial fibrosis. We have recently shown, using this model, that mice lacking the bradykinin B2-receptor (B2-/- ) were more susceptible than control animals to the development of tubulointerstitial fibrosis. Angiotensin converting enzyme (ACE) inhibition slows down UUO-induced renal fibrosis. Since ACE-inhibition increases bradykinin and decreases angiotensin II concentrations we have verified if bradykinin is involved in the antifibrotic effects of ACE-inhibition using the UUO-model and B2-/- mice. Surprisingly, although ACE-inhibition significantly reduced renal fibrosis, no difference was observed between the degree of tubulointerstitial fibrosis, macrophage infiltration and cell proliferation between ACE-inhibitor treated B2+/+ and B2-/- mice suggesting the absence of a role of the B2-receptor in the antifibrotic effects of ACE-inhibition. This was confirmed at the level of bradykinin-induced activity of enzymes involved in the degradation of the extracellular matrix. However in both mouse strains, ACE-inhibitors were more efficient than AT1 receptor antagonists.Theme paper: Part of this paper was originally presented at the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.

Effect of angiotensin-converting-enzyme inhibition on bradykinin metabolism by vascular endothelial cells

1993 ◽  
Vol 264 (5) ◽  
pp. H1493-H1497 ◽  
Author(s):  
M. Grafe ◽  
C. Bossaller ◽  
K. Graf ◽  
W. Auch-Schwelk ◽  
C. R. Baumgarten ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Angiotensin Converting Enzyme ◽  
Vascular Endothelial Cells ◽  
Ace Inhibition ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Dependent Manner ◽  
Converting Enzyme ◽  
Concentration Dependent Manner ◽  
Cell Monolayers ◽  
Converting Enzyme Inhibition

The degradation of bradykinin by angiotensin-converting-enzyme (ACE) activity in cultured human endothelial cells was studied by direct measurement of bradykinin and by its effect on the release of endothelium-derived relaxing factors. The half-life of exogenous bradykinin (10,000 pg/ml) was calculated from the decay of the bradykinin concentration as 46 +/- 2 min in cell monolayers, 133 +/- 15 min in conditioned medium, and 24 +/- 2 min in homogenates. Most of the bradykinin-degrading activity in cell monolayers could be inhibited in a concentration-dependent manner by the ACE inhibitors lisinopril, ramiprilat, and captopril. Bradykinin-degrading activity was released into the culture medium containing one-fourth of the bradykinin-degrading activity found in the presence of cell monolayers. In cell homogenates higher unspecific bradykinin-degrading activities were present. The functional consequence of bradykinin degradation was demonstrated by the potentiating effect of ramiprilat on the generation of endothelium-derived relaxing factors nitric oxide and prostacyclin from endothelial cells. The study supports the concept of increased vasodilatory effects of bradykinin during ACE inhibition.

scholarly journals ANGIOTENSIN CONVERTING ENZYME INHIBITION POTENTIAL OF ANNAPAVALA CHENDHURAM FOR THE TREATMENT OF HYPERTENSION - AN IN–VITRO ASSAY

AYUSHDHARA ◽  
2020 ◽  
pp. 2599-2604
Author(s):  
Sabari Girija N ◽  
Sinekha M A ◽  
Guptaj S ◽  
Shanmugapriya P ◽  
Madhavan R
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Ace Inhibition ◽  
In Vitro Assay ◽  
Lifestyle Changes ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Uv Spectrophotometry ◽  
Test Drug ◽  
Converting Enzyme ◽  
Vitro Assay

Hypertension is that the most noteworthy risk factor for cardiovascular diseases and stroke. Dietary and lifestyle changes play the foremost part to decrease the hazard of hypertension and other related wellbeing complications. Angiotensin Converting Enzyme (ACE) inhibitors play a major role in treating hypertension. Annapavala chendhuram is a herbo – mineral Siddha formulation comes under the type of 32 internal medicines of Siddha. Hypolipidemic activity of Annapavala chendhuram has been proven by some research studies. Hence, the purpose of the present study was to evaluate the ACE inhibition activity on Annapavala chendhuram by using an in-vitro assay. The ACE inhibition assay was evaluated by UV Spectrophotometry technique based on the hydrolysis of histidyl-hippuryl-leucine (HHL) by ACE. About 50µL test sample with varying concentration (100- 500 µg/ml) along with standard captopril (100µg/ml) added with 50µL of ACE and some process had continued. The present study indicates that the test drug Annapavala chendhuram was effective in inhibiting the enzyme ACE dose-dependently. Maximum percentage inhibition of about 53.24±8.403% was observed at 500μg/ml when compared to that of the Captopril, a standard ACE enzyme inhibitor agent with the maximum inhibition 86.98 ± 6.375 at the concentration of 100μg/ml. It was concluded that the test drug Annapavala chendhuram possess significant anti-hypertensive property in protein denaturation assay. So, further in-vitro evaluation of ACE inhibitory activity on Siddha herbal preparations and clinical trials will be the need of the hour.

Abstract 230: Angiotensin-Converting Enzyme Inhibition Increases ADMA Concentration in Patients on Hemodialysis

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Jorge L Gamboa ◽  
Mias Pretorius ◽  
Talat A Ikizler ◽  
Nancy J Brown
Keyword(s):  
Endothelial Dysfunction ◽  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blockers ◽  
A549 Cells ◽  
Ace Inhibition ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Dialysis Session ◽  
Converting Enzyme ◽  
Cardiovascular Morbidity And Mortality ◽  
Adma Concentration

Endothelial dysfunction occurs commonly in patients with end-stage renal disease (ESRD) and is associated with increased cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA), an inhibitor of nitric oxidase synthase, is elevated in patients with chronic kidney disease and contributes to endothelial dysfunction in ESRD. In the general population, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) decrease ADMA levels, but no study has compared the effect of these drugs in patients with ESRD on hemodialysis. We therefore evaluated the effect of one-week treatment with ramipril (5 mg/d), valsartan (160 mg/d) and placebo on ADMA levels in fifteen patients on hemodialysis in a previously published double-blind, placebo-controlled, 3X3 cross-over study. We found that ADMA levels were increased at baseline and throughout the dialysis session during ramipril treatment (Figure 1, p<0.001 compared to both placebo and valsartan). Ramipril did not increase ADMA levels in a study of patients without ESRD, suggesting that factors related to ESRD or hemodialysis contribute to the ACE inhibitor-induced increase in ADMA levels. We have previously shown that ACE inhibition increases bradykinin (BK) levels during hemodialysis. Therefore, we evaluated the effect of BK on ADMA production in A549 cells; incubation with BK increased intracellular ADMA concentration through bradykinin B2- receptor (B2R) stimulation (Figure 2). In conclusion, ACE inhibition increases ADMA in patients on hemodialysis. Studies in vitro suggest that this could occur through a bradykinin-mediated increase in ADMA production.

scholarly journals Angiotensin-converting enzyme governs endogenous opioid signaling and synaptic plasticity in nucleus accumbens

2021 ◽  
Author(s):  
Brian H. Trieu ◽  
Bailey C. Remmers ◽  
Carlee Toddes ◽  
Dieter D. Brandner ◽  
Wei Xie ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Angiotensin Converting Enzyme ◽  
Glutamate Release ◽  
Ace Inhibition ◽  
Receptor Activation ◽  
Projection Neurons ◽  
Converting Enzyme ◽  
Endogenous Opioid ◽  
Central Function ◽  
Opioid Signaling

AbstractAngiotensin-converting enzyme (ACE) regulates blood pressure by cleaving angiotensin I to produce angiotensin II. In the brain, ACE is expressed at uniquely high levels in the striatonigral pathway, but its central function remains poorly understood. We find that ACE degrades an unconventional enkephalin heptapeptide, Met-enkephalin-Arg-Phe, in the nucleus accumbens of mice. ACE inhibition enhanced mu opioid receptor activation by Met-enkephalin-Arg-Phe, causing a cell type-specific long-term depression of glutamate release onto medium spiny projection neurons expressing the Drd1 dopamine receptor. Systemic ACE inhibition was not intrinsically rewarding, but decreased the conditioned place preference caused by fentanyl administration, and enhanced reciprocal social interaction. Our results raise the enticing prospect that central ACE inhibition can boost endogenous opioid signaling for clinical benefit, while mitigating risk of addiction.

Combined angiotensin-converting enzyme inhibition and adrenomedullin in an ovine model of heart failure

2002 ◽  
Vol 102 (6) ◽  
pp. 653-660 ◽  
Author(s):  
Miriam T. RADEMAKER ◽  
Chris J. CHARLES ◽  
Garth J.S. COOPER ◽  
David H. COY ◽  
Eric A. ESPINER ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Cardiac Output ◽  
Angiotensin Converting Enzyme ◽  
Creatinine Clearance ◽  
Ace Inhibitor ◽  
Ace Inhibition ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
Creatinine Excretion

Advances in the treatment of heart failure may require manipulation of neurohumoral responses to cardiac impairment in addition to the established strategy of angiotensin-converting enzyme (ACE) inhibition. Importantly, since new treatments are likely to be used in conjunction with ACE inhibition therapy, the effects of the combination of agents need to be assessed. Adrenomedullin (ADM) is a peptide with potent vasodilator and natriuretic actions. ADM and an ACE inhibitor (captopril) were administered for 3h both separately and together in eight sheep with heart failure. Both ADM and captopril alone reduced arterial pressure, left atrial pressure (greater with captopril) and peripheral resistance, and increased cardiac output (greater with ADM). Compared with either treatment separately, combined ADM+captopril produced directionally similar but significantly greater changes in all haemodynamic variables (particularly falls in blood pressure). ADM increased renal sodium and creatinine excretion and creatinine clearance, and maintained urine output. Captopril and ADM+captopril reduced creatinine excretion and creatinine clearance, while urine volume and sodium excretion were not significantly altered. Plasma renin activity rose with all active treatments, whereas angiotensin II levels rose during ADM, but fell during captopril and ADM+captopril. Aldosterone was reduced by all active treatments. ADM+captopril reduced plasma noradrenaline (norepinephrine). In conclusion, short-term co-treatment with ADM and an ACE inhibitor produced significantly greater decreases in ventricular filling pressures and cardiac afterload, and increases in cardiac output, compared with either treatment alone. Despite the greater falls in blood pressure (and presumably renal perfusion pressure), renal function was maintained at a level similar to that observed with captopril alone.

scholarly journals Angiotensin Converting Enzyme Inhibition Activity of Fennel and Coriander Oils from India

2013 ◽  
Vol 8 (5) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Sushil Kumar Chaudhary ◽  
Niladri Maity ◽  
Neelesh Kumar Nema ◽  
Santanu Bhadra ◽  
Bishnu Pada Saha ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Ace Inhibitor ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Ace Inhibition ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
Foeniculum Vulgare ◽  
Converting Enzyme Inhibition ◽  
Dpph Radical Scavenging

Foeniculum vulgare Mill and Coriandrum sativum L. are very popular spices in Indian kitchens. The present study was an attempt to evaluate the angiotensin converting enzyme (ACE) inhibition and antioxidant activity of the standardized oils of F. vulgare and C. sativum by an UV method using hippuryl-L-histidyl-L-leucine (HHL) as substrate. Standardization of the oils and identification of the chemical-markers (linalool and anethole) present in them was performed through HPLC and GC-MS. Coriander oil showed the higher ACE inhibition with an IC50 value of 34.8 ± 2.3 μg/mL, than fennel oil with an IC50 value of 40.7 ± 3.5 μg/mL. Both oils showed strong DPPH radical scavenging activity. This finding suggests that coriander and fennel oils can be potential leads for the management of hypertension as an ACE inhibitor.

Structural basis for the C-domain-selective angiotensin-converting enzyme inhibition by bradykinin-potentiating peptide b (BPPb)

2019 ◽  
Vol 476 (10) ◽  
pp. 1553-1570 ◽  
Author(s):  
Edward D. Sturrock ◽  
Lizelle Lubbe ◽  
Gyles E. Cozier ◽  
Sylva L.U. Schwager ◽  
Afolake T. Arowolo ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Domain Structure ◽  
Ace Inhibitors ◽  
Ace Inhibition ◽  
Site Directed Mutagenesis ◽  
Structural Basis ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
X Ray Crystallography

Abstract Angiotensin-converting enzyme (ACE) is a zinc metalloprotease best known for its role in blood pressure regulation. ACE consists of two homologous catalytic domains, the N- and C-domain, that display distinct but overlapping catalytic functions in vivo owing to subtle differences in substrate specificity. While current generation ACE inhibitors target both ACE domains, domain-selective ACE inhibitors may be clinically advantageous, either reducing side effects or having utility in new indications. Here, we used site-directed mutagenesis, an ACE chimera and X-ray crystallography to unveil the molecular basis for C-domain-selective ACE inhibition by the bradykinin-potentiating peptide b (BPPb), naturally present in Brazilian pit viper venom. We present the BPPb N-domain structure in comparison with the previously reported BPPb C-domain structure and highlight key differences in peptide interactions with the S4 to S9 subsites. This suggests the involvement of these subsites in conferring C-domain-selective BPPb binding, in agreement with the mutagenesis results where unique residues governing differences in active site exposure, lid structure and dynamics between the two domains were the major drivers for C-domain-selective BPPb binding. Mere disruption of BPPb interactions with unique S2 and S4 subsite residues, which synergistically assist in BPPb binding, was insufficient to abolish C-domain selectivity. The combination of unique S9–S4 and S2′ subsite C-domain residues was required for the favourable entry, orientation and thus, selective binding of the peptide. This emphasizes the need to consider factors other than direct protein–inhibitor interactions to guide the design of domain-selective ACE inhibitors, especially in the case of larger peptides.

Angiotensin-converting enzyme inhibition attenuates myonuclear addition in overloaded slow-twitch skeletal muscle

2005 ◽  
Vol 289 (4) ◽  
pp. R1223-R1231 ◽  
Author(s):  
Christopher M. Westerkamp ◽  
Scott E. Gordon
Keyword(s):  
Skeletal Muscle ◽  
Angiotensin Converting Enzyme ◽  
Ace Inhibition ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Sham Operation ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Surgical Ablation ◽  
Slow Twitch ◽  
Fast Twitch

Because optimal overload-induced skeletal muscle hypertrophy requires ANG II, we aimed to determine the effects of blocking ANG II production [via angiotensin-converting enzyme (ACE) inhibition] on potential mediators of hypertrophy in overloaded skeletal muscle, namely, myonuclear addition and fibroblast content. In a 2 × 2 design, adult (200–225 g) female Sprague-Dawley rats were placed into one of four groups ( n = 8/group): 7-day skeletal muscle overload, sham operation, 7-day skeletal muscle overload with ACE inhibition, or sham operation with ACE inhibition. Functional overloads of the plantaris and soleus muscles were produced via bilateral surgical ablation of the synergistic gastrocnemius muscle, and ACE inhibition was accomplished by the addition of the ACE inhibitor enalapril maleate to the animals' daily drinking water (0.3 mg/ml). Myonuclear addition and extrasarcolemmal nuclear proliferation, as measured by in vivo 5-bromo-2′-deoxyuridine labeling, were significantly ( P ≤ 0.05) increased by overload in both the slow-twitch soleus and fast-twitch plantaris muscles. Furthermore, ACE inhibition attenuated these overload-induced increases in the soleus muscle but not in the plantaris muscle. However, the effect of ACE inhibition on soleus extrasarcolemmal nuclei was not likely due to differences in fibroblast content because overload elicited significant increases in vimentin-positive areas in soleus and plantaris muscles, and these areas were unaffected by ACE inhibition in either muscle. There was no effect of ACE inhibition on any measure in sham-operated muscles. Collectively, these data indicate that ANG II may mediate the satellite cell response to overload in slow-twitch soleus but not in fast-twitch plantaris muscles and that this effect may occur independently of changes in fibroblast content.

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