Renin inhibitors. Free-Wilson and correlation analysis of the inhibitory potency of a series of pepstatin analogs on plasma renin

1987 ◽  
Vol 30 (12) ◽  
pp. 2287-2291 ◽  
Author(s):  
Dino Nisato ◽  
Jean Wagnon ◽  
Georges Callet ◽  
Daniel Mettefeu ◽  
Jean Louis Assens ◽  
...  
Keyword(s):  
Correlation Analysis ◽  
Plasma Renin ◽  
Inhibitory Potency ◽  
Renin Inhibitors

Renin inhibitors. Dipeptide analogs of angiotensinogen utilizing a dihydroxyethylene transition-state mimic at the scissile bond to impart greater inhibitory potency

1988 ◽  
Vol 31 (12) ◽  
pp. 2264-2276 ◽  
Author(s):  
Jay R. Luly ◽  
Nwe BaMaung ◽  
Jeff Soderquist ◽  
Anthony K. L. Fung ◽  
Herman Stein ◽  
...  
Keyword(s):  
Transition State ◽  
Inhibitory Potency ◽  
Renin Inhibitors ◽  
Scissile Bond

Effects of Angiotensinase Inhibitors on Plasma Protein Binding and IC50 Determinations of Renin Inhibitors

1992 ◽  
Vol 38 (11) ◽  
pp. 2239-2243 ◽  
Author(s):  
B D Dayton ◽  
H H Stein ◽  
J Cohen ◽  
W R Baker ◽  
S A Boyd ◽  
...  
Keyword(s):  
Plasma Renin Activity ◽  
Plasma Proteins ◽  
Proteinase Inhibitors ◽  
Plasma Renin ◽  
Renin Activity ◽  
Phenylmethylsulfonyl Fluoride ◽  
Renin Inhibitors ◽  
Ic50 Values

Abstract To establish whether the use of proteinase inhibitors in the routine determination of in vitro plasma renin activity overestimates the potency of renin inhibitors in vivo, we examined the effects of phenylmethylsulfonyl fluoride and 8-hydroxyquinoline sulfate on the binding to plasma proteins and the respective IC50 values (50% inhibiting concentrations) of three renin inhibitors. All three renin inhibitors, A-64662, A-65317, and A-74273, bound (> 60%) to plasma proteins at both pH 6.0 and 7.4, with slightly greater binding at pH 7.4. Phenylmethylsulfonyl fluoride (1.45 mmol/L) had no significant effect on the protein binding at either pH 6.0 or 7.4; 8-hydroxyquinoline sulfate (3.4 mmol/L) caused a modest dissociation (10-30%) of the renin inhibitors from plasma proteins at both pH values; and the effects of both proteinase inhibitors together were similar to those of 8-hydroxyquinoline alone. At pH 7.4, phenylmethylsulfonyl fluoride increased the potencies of the three renin inhibitors slightly (< or = 43%), whereas IC50 values determined in the presence of 8-hydroxyquinoline decreased by 1.5- to 3.7-fold. The greatest increase in potency occurred with the most hydrophilic compound, and with both angiotensinase inhibitors the effect was no greater than that of 8-hydroxyquinoline alone. The results show that any dissociation of the hypotensive activity measured in vivo from the plasma renin activity measured in vitro is not simply an artifact in the plasma renin activity assay stemming from the use of these angiotensinase inhibitors, especially if only phenylmethylsulfonyl fluoride is used.

Hypertension Management and End Organ Protection: Focus on Aliskiren

2009 ◽  
Vol 1 ◽  
pp. CMT.S1980
Author(s):  
Toshio Imanishi ◽  
Hiroto Tsujioka ◽  
Takashi Akasaka
Keyword(s):  
Ace Inhibitors ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Renin Inhibitor ◽  
Organ Protection ◽  
Renin Inhibitors ◽  
Direct Renin Inhibitor ◽  
Key Factor ◽  
Receptor Blockers

The renin-angiotensin system (RAS) activity is a key factor in the pathophysiology and development of hypertension, atherosclerosis, heart failure, and renal disease. It is unclear whether angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) have fully delivered the expected reductions in cardiovascular risk. In fact, the optimized RAS suppression is difficult to achieve with these agents, partly because ACE inhibitors and ARBs both activate compensatory feedback mechanisms that result in renin release and increase plasma renin activity (PRA). Molecular modeling was used to develop aliskiren, a potent, low-molecular-weight, nonpeptide, direct renin inhibitor with sufficient bioavailability to produce sustained suppression of PRA after oral administration. This report discusses the mechanisms of action of oral renin inhibitors and their pharmacokinetic properties. In addition, the report also evaluates the available data regarding the effects of the renin inhibitor aliskiren in the treatment of hypertension and related cardiovascular disorders.

Good News from Aliskiren?

2009 ◽  
Vol 1 ◽  
pp. CMT.S2862
Author(s):  
Paolo Verdecchia ◽  
Fabio Angeli ◽  
Gianpaolo Reboldi
Keyword(s):  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Tissue Level ◽  
Good News ◽  
Angiotensin Ii Receptor ◽  
Angiotensin I ◽  
Converting Enzyme Inhibitors ◽  
Renin Inhibitors

The renin-angiotensin system can be inhibited through inhibition of angiotensin I generation from angiotensinogen by direct renin inhibitors, inhibition of angiotensin II generation from angiotensin I by angiotensin-converting enzyme inhibitors and by direct inhibition of the action of angiotensin II receptor level. Aliskiren, the first direct renin inhibitor to reach the market, is a low molecular weight, orally active, hydrophilic nonpeptide. It blocks angiotensin I generation, while plasma renin concentration increases because the drugs blocks the negative feed-back exerted by angiotensin II on renin synthesis. Aliskiren is suitable for once-daily administration because of its long pharmacological half-life. Because of its mechanism of action, aliskiren may provide the additional opportunity to inhibit progression of atherosclerosis at tissue level. Hypertension is an approved indication for aliskiren, which is also promising for the treatment of heart failure and diabetic nephropathy. The efficacy of this drug on major clinical events is being tested in large ongoing clinical trials.

Microdensitometer—computer correlation analysis of ultrastructural periodicity

1978 ◽  
Vol 36 (2) ◽  
pp. 32-33
Author(s):  
D.R. Ensor ◽  
C.G. Jensen ◽  
J.A. Fillery ◽  
R.J.K. Baker
Keyword(s):  
Correlation Analysis ◽  
Background Noise ◽  
Computer Control ◽  
Optical Diffraction ◽  
Screw Thread ◽  
Straight Line ◽  
Computer Storage ◽  
Correlation Process ◽  
Electron Microscope Image ◽  
Fixed Beam

Because periodicity is a major indicator of structural organisation numerous methods have been devised to demonstrate periodicity masked by background “noise” in the electron microscope image (e.g. photographic image reinforcement, Markham et al, 1964; optical diffraction techniques, Horne, 1977; McIntosh,1974). Computer correlation analysis of a densitometer tracing provides another means of minimising "noise". The correlation process uncovers periodic information by cancelling random elements. The technique is easily executed, the results are readily interpreted and the computer removes tedium, lends accuracy and assists in impartiality.A scanning densitometer was adapted to allow computer control of the scan and to give direct computer storage of the data. A photographic transparency of the image to be scanned is mounted on a stage coupled directly to an accurate screw thread driven by a stepping motor. The stage is moved so that the fixed beam of the densitometer (which is directed normal to the transparency) traces a straight line along the structure of interest in the image.

Effects of renovascular hypertension on rat adrenal zona glomerulosa

1978 ◽  
Vol 36 (2) ◽  
pp. 582-583
Author(s):  
G. Mazzocchi ◽  
P. Rebuffat ◽  
C. Robba ◽  
P. Vassanelli ◽  
G. G. Nussdorfer
Keyword(s):  
Renovascular Hypertension ◽  
Left Kidney ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Zona Glomerulosa ◽  
Ultrastructural Changes ◽  
Albino Rats ◽  
Left Renal Artery ◽  
Angiotensin System ◽  
And Control

It is well known that the rat adrenal zona glomerulosa steroidogenic activity is controlled by the renin-angiotensin system. The ultrastructural changes in the rat zona glomerulosa cells induced by renovascular hypertension were described previously, but as far as we are aware no correlated biochemical and morphometric investigations were performed.Twenty adult male albino rats were divided into 2 experimental groups. One group was subjected to restriction of blood flow to the left kidney by the application of a silver clip about the left renal artery. The other group was sham-operated and served as a control. Renovascular hypertension developed in about 10 days: sistolic blood pressure averaged 165 ± 6. 4 mmHg, whereas it was about 110 ± 3. 8 mmHg in the control animals. The hypertensive and control rats were sacrificed 20 days after the operation. The blood was collected and plasma renin activity was determined by radioimmunological methods. The aldosterone concentration was radioimmunologically assayed both in the plasma and in the homogenate of the left capsular adrenal gland.

The German Strengths and Difficulties Questionnaire (SDQ)

2010 ◽  
Vol 26 (4) ◽  
pp. 256-262 ◽  
Author(s):  
Ulrike Petermann ◽  
Franz Petermann ◽  
Ina Schreyer
Keyword(s):  
Correlation Analysis ◽  
Teacher Ratings ◽  
Screening Instrument ◽  
Preschool Age ◽  
Strengths And Difficulties Questionnaire ◽  
Preschool Age Children ◽  
Discriminant Analyses ◽  
Strengths And Difficulties ◽  
Behavioral Attributes ◽  
And Behavior

The Strengths and Difficulties Questionnaire (SDQ) is a screening instrument that addresses positive and negative behavioral attributes of children and adolescents. Although this questionnaire has been used in Germany to gather information from parents and teachers of preschoolers, few studies exist that verify the validity of the German SDQ for this age. In the present study, teacher ratings were collected for 282 children aged 36 to 60 months (boys = 156; girls = 126). Likewise, teacher ratings were collected with another German checklist for behavior problems and behavior disorders at preschool age (Verhaltensbeurteilungsbogen für Vorschulkinder, VBV 3–6). Moreover, children’s developmental status was assessed. Evaluation included correlation analysis as well as canonical correlation analysis to assess the multivariate relationship between the set of SDQ variables and the set of VBV variables. Discriminant analyses were used to clarify which SDQ variables are useful to differentiate between children with or without developmental delay in a multivariate model. The results of correlation and discriminant analyses underline the validity of the SDQ for preschoolers. According to these results, the German teacher SDQ is recommended as a convenient and valid screening instrument to assess positive and negative behavior of preschool age children.

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