Angiotensin I converting enzyme and the changes in our concepts through the years. Lewis K. Dahl memorial lecture.

Erdös, Ervin G.

doi:10.1161/01.hyp.16.4.363

Cited by 405 publications

(225 citation statements)

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“…The discrepancy between positive and negative results might come from variations in the ethnic groups studied, from differences in the severity of hypertension in the affected patients studied, or Previous studies have shown that the I/D polymorphism in the ACE gene accounts for half of the variance of serum ACE levels. 26 Since ACE mediates the conversion of AT-I to AT-II, 2 and the D allele of the ACE gene is a marker for high levels of circulating ACE, 3,27 and since AT-II receptors are typical G-protein-coupled receptors, 28 thus it may be plausible that a gene variant associate with increased serum ACE concentrations (ACE D allele) may become pathophysiologically important in individuals whose genetic makeup comprises an allelic variant that causes an increased cell responsiveness. In this respect, the GNB3 825T allele represents an attractive candidate to interact with the ACE D allele.…”

Section: Discussionmentioning

confidence: 99%

“…Angiotensin-converting enzyme (ACE), an important component of the rennin-angiotensin system, regulates BP by activating an inactive angiotensin I (AT-I) into a potent vasopressor, angiotensin II (AT-II), and inactivating a potent vasodilator, bradykinin. 2 Since Rigat et al 3 identified a biallelic polymorphism in the ACE gene that is characterized by either the absence (deletion D) or presence (insertion I) of a 287-bp Alu repeat sequence, several studies have shown an association of ACE genotype with BP, 4,5 whereas other studies have not. [6][7][8] G-protein is a heterotrimeric protein that consists of a-, b-, and gsubunits.…”

Section: Introductionmentioning

confidence: 99%

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GNB3 gene C825T and ACE gene I/D polymorphisms in essential hypertension in a Kazakh genetic isolate

Wang

Lin

et al. 2004

J Hum Hypertens

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The Kazakh inhabitants living in Barkol pasture of northeast China belong to a genetic isolate characterized by ethnically homogeneous and a communal pastoral lifestyle. To investigate whether the polymorphisms in the G-protein b-3 subunit (GNB3) gene and angiotensin-converting enzyme (ACE) gene are associated with essential hypertension (EH), we carried out a case-control study of 290 hypertensive subjects and 244 normotensive (NT) controls randomly selected from Kazakh populations of Barkol. A previous medical history of diabetes and hypertension, and body mass index (BMI) was recorded. Plasma glucose, triglyceride, and cholesterol were measured. The insertion/deletion (I/D) polymorphism of the ACE gene and the C825T polymorphism of the GNB3 gene were determined by the polymerase chain reaction (PCR) technique. The distributions of genotypes and alleles for the two polymorphisms did not differ significantly between the case and control populations, and odds ratio of EH related to the ACE gene D allele and GNB3 gene T allele was not significantly different from 1.0. Logistic regression analysis shows the variation at the GNB3 and ACE did not have any statistically significant synergistic effect on blood pressure (BP). Stratification of NT and untreated hypertensives according to I/D polymorphism of ACE gene and C825T polymorphism of GNB3 gene disclosed no significant difference across genotypes with respect to BMI, glucose, triglyceride, cholesterol, systolic and diastolic BP. In conclusion, the polymorphisms in the GNB3 gene and ACE gene, solely or combined, did not confer a significantly increased risk for the development of EH in the Kazakh isolate of northeast China.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

GNB3 gene C825T and ACE gene I/D polymorphisms in essential hypertension in a Kazakh genetic isolate

Wang

Lin

et al. 2004

J Hum Hypertens

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“…Angiotensin-converting enzyme (ACE) is a transmembrane glycoprotein expressed on the endothelial luminal surface, which converts Ang I into Ang II to induce vasoconstricting, pro-oxidant and pro-inflammatory activities [61][62][63]. Pulmonary vasculature is enriched in …”

Section: Endothelial Surface Determinants: Potential Targets For Drugmentioning

confidence: 99%

“…Interestingly, one modality of a vasoactive agent (e.g., its effect on blood pressure) frequently is balanced by its other modality (effect on permeability). For example, endothelial ACE converts Ang I into Ang II, which induces vasoconstriction, yet ACE also inactivates bradykinin and substance P [61], peptides that increase vascular permeability. EC produce a potent vasodilating agent NO that may reduce vascular permeability at low levels [297].…”

Section: Traversing Endothelial Barriers Via Transcytosis and Paracelmentioning

confidence: 99%

Targeting of Drugs to ICAM for Treatment of Acute Lung Injury

Muzykantov¹

2004

PsycEXTRA Dataset

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_ Public reporting burden for this coliection of information is estimated to average 1 tiour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining " the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing Uiis bunjen to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highv^ay, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Papenrork Reduction Project (0704-0188), Washington, DC 20503 AGENCY USE ONLY (Leave blank) REPORT DATE April 2004 REPORT TYPE AND DATES COVERED Annual (11 Mar 2003 -10 Mar 2004) TITLE AND SUBTITLE Targeting of Drugs to ICAM for Treatment of Acute Lung Injury AUTHOR(S)Vladimir Muzykantov, Ph.D. FUNDING NUMBERS DAMD17-02-1-0197 PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)University of Pennsylvania Philadelphia, PA 19104-6205 E-Mail: muzykantOmail. med. upenn. edu PERFORMING ORGANIZATION REPORT NUMBER SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSORING / MONITORING AGENCY REPORT NUMBER SUPPLEMENTARY NOTESOriginal contains color plates: ALL DTIC reproductions will be in black and white 12a. DISTRIBUTION / AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 12b. DISTRIBUTION CODE ABSTRACT (Maximum 200 Words)In the second year, we characterized intracellular traffic and final destination of anti-CAM conjugates in endothelial cells (EC) and found that CAM-mediated endocytosis initiates an unusually slow vesicular traffic that delivers conjugates to lysosomes several hours after internalization. Further, auxiliary drugs that regulate these processes can be utilized for prolongation of therapeutic duration of internalized conjugates. We characterized a series of in-house models of human ALI (injection of anti-TM/GOX and hyperoxia in mice), studied dynamics and role of EC cell adhesion molecules and leukocytes in these models and developed a new, clinically relevant and reliable model of ALI, based on combined treatment with anti-TM/GOX and hyperoxia. We synthesized anti-CAM/SOD conjugate with proper targeting size (~200 nm), enzymatic activity and affinity to EC and documented that it accumulates in the pulmonary vasculature after intravenous injection, thus satisfying main requirements for subsequent testing in animal models of ALI. In vitro and in vivo fibrinolysis studies have been employed in order to select the optimal candidate fibrinolytic (a novel tPA derivative, Tenektase) for targeting to endothelial CAM. Design and production of optimized affinity carriers for this purpose is in progress. SUBJECT TERMSEndothelium, immunotargeting, oxidant stress, thrombosis, ICAM-1 Vladimir Muzykantov, PI, DAMD 17-02-1-0197 "ICAM Targeting in Acute Lung Injury" Second Annual ...

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“…Angiotensin con verting enzyme (ACE) inhibitors have been used for more than a decade in the clinical treatment of hypertension, and they have also been used with favorable effects on con gestive heart failure (1, 2). However, ACE cleaves not only angiotensin I (Ang I), but also hydrolyzes brady kinin, substance P and enkephalins (3,4), so the blockade of ACE may cause side effects such as dry cough (5). Ac cordingly, selectively preventing the binding of angioten sin II (Ang II) to the receptor would provide a safe and rational way to block the RAS.…”

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confidence: 99%

The Pharmacological Characterization of FK 739, a New Angiotensin II-Receptor Antagonist

Hamada¹,

Nakajima²,

Nirei³

et al. 1993

Japanese Journal of Pharmacology

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ABSTRACT-The pharmacological properties of FK 739, a new angiotensin 11-receptor antagonist, were ex amined. FK 739 inhibited the specific binding of [125I1-angiotensin II to rat aortic smooth muscle cell mem brane with an IC50 value of 8.6 nM, but did not displace the specific binding of [1151] -angiotensin II to bovine cerebellum membrane. In isolated helical strips of rabbit aorta, FK 739 shifted the concentration response curve of angiotensin II-induced contraction in parallel to the right, and the values of the slope and pA2 were 1.06 and 8.45, respectively. In in vivo studies, oral administration of FK 739 at 10 mg/kg sig nificantly inhibited the angiotensin I-induced pressor response in normotensive rats and dogs, and it caused a fall of mean blood pressure in renal hypertensive rats and dogs. In spontaneously hypertensive rats, FK 739 at 32 and 100 mg/kg significantly decreased the mean blood pressure in a dose-dependent manner. Additionally, we studied whether FK 739 would cause side effects such as dry cough, like other ACE in hibitors did. Oral administration of FK 739 (10 and 32 mg/kg) did not affect the capsaicin-induced bron chial edema. On the other hand, captopril (10 mg/kg) significantly enhanced capsaicin-induced bronchial edema. These results indicate that FK 739 is a potent and competitive antagonist for AT,-type receptors, and suggest that FK 739 might be a safe and useful agent for the treatment of hypertension in clinical trials.

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Angiotensin I converting enzyme and the changes in our concepts through the years. Lewis K. Dahl memorial lecture.

Cited by 405 publications

References 53 publications

GNB3 gene C825T and ACE gene I/D polymorphisms in essential hypertension in a Kazakh genetic isolate

GNB3 gene C825T and ACE gene I/D polymorphisms in essential hypertension in a Kazakh genetic isolate

Targeting of Drugs to ICAM for Treatment of Acute Lung Injury

The Pharmacological Characterization of FK 739, a New Angiotensin II-Receptor Antagonist

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