Renin inhibition

Renal Decreased Na+ and HjO excretion, renal failure, decreased effectiveness of diuretics and antihypertensives PGE2- and PGb-induced vasodilation in juxtamedullary apparatus (increases renal blood flow, antagonizes renin, inhibits reabsorption of Na+ and HjO) cox-1 cox-2... 

Renin inhibition has thus proved to be an important new approach to the treatment of hypertension. 

Padia S, Siragy H Renin inhibition as a new strategy to combat cardiovascular disease. Curr Hypertens Rev 2007 3 39. 

Pool JL Direct renin inhibition Focus on aliskiren. J Manag Care Pharm 2007 13(Suppl B) 21. 

Villamil A et al Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide. J Hypertens 2007 25 217. [PMID 17143194]... 

Aliskiren is presently being evaluated in the ASPIRE HIGHER clinical trial program in more than 35,000 patients in 14 trials to study the effect of renin inhibition on outcomes in patients with conditions such as heart failure and diabetes as well as on organ protection benefit in a variety of disease states.25 To date, three of the short-term trials with organ protection endpoints have reported findings. In patients with type 2 diabetese, kidney disease, and high blood pressure, the AVOID (Aliskiren in the Evaluation of Proteinuria in Diabetes) study has demonstrated that aliskiren provides additional kidney protection when added to the maximum dose of the ARB losartan.26 In... 

Shaflq MM, Menon DV, Victor RG. Oral direct renin inhibition premise, promise, and potential limitations of a new antihypertensive drug. Am. J. Med. 2008 121 265-271. 

Glycoconjugate inhibitors of the renin aspartyl protease have also been formulated for increased solubility and altered clearance. Known peptide inhibitors were conjugated to either GlcNAc or mannose, and then evaluated for renin inhibition [191] (O Fig. 15). 

N-chlorocarbonyl morpholine has found some valuable applications to convert amino acids to N-morpholinocar-bonyl amino acids, for example N-morpholinocarbonyl-(L)-phenylalanine [Scheme 120] for the preparation of renin-inhibiting peptides. 

Kleinert, H.D, (1995) Renin inhibition. Cardiovasc. Drugs Ther., 9.645-655. Rosenberg. S.H. (1995) Renin Inhibitors. Prog. Med. Chem.. 32. 37-114. 

Figure 10-11. Angiotensinogen scission and renin inhibition (see text for discussion).

Current approaches to renin inhibition have been reviewed. Monoclonal antibodies with high affinity and specificity for human renin have been developed and several new peptides modeled after the minimal substrate oc-tapeptlde ( 1) have been prepared. 

Figure 8.14 Combining structural features of two renin inhibitors, 2 and 4, to produce a hybrid structure, 5, combining the best of both. Renin inhibition IC50 values are listed below the compound numbers. (Holsworlh, D.D. Discovery of 6-elhyl-2,4-diaminopyrimidine-based small molecule renin inhibitors.

ALTITUDE Hans-Henrik Parving Novartis Effect on renin-inhibition on high -risk diabetic patients T2 DM patients (8,600) 2008... 

Stanton, A. 2003. Potential of renin inhibition in cardiovascular disease. J. Renin Agntiotensin Aldosterone Syst. 4 6-10. 

Yuan, L., Wu, J., Aluko, R., and Ye, X. 2006. Kinetics of renin inhibition by sodium houttuyfonate analogs. Biosci. Biotechnol. Biochem. 70 2275-2280. 

Pinto R, Gradman AH. Direct renin inhibition an update. Curr Hypertens Rep 2009 11(6) 456-62. 

Tapaninen T, Neuvonen PJ, Niemi M. Rifampicin reduces the plasma concentrations and the renin-inhibiting effect of ahskiren. Eur J Chn Pharmacol 2010 66(5) 497-502. 

Rashid H. Direct renin inhibition an evaluation of the safety and tolerability of aliskiren. Curr Med Res Opin 2008 24(9) 2627-37. 

Renin inhibition analogs Transition state inhibitors 326/1993... 

Muller DN, Luft FC. Direct renin inhibition with aliskiren in h3fpertension and target organ damage CUn. J. Am. Soc. Nephrol. 2006 1 221-228. 

Sureshkumar KK. Renin inhibition with aliskiren in hypertension focus on aliskiren/hydrochlorothiazide combination therapy. Vase. Health Risk Manag. 2008 4(6) 1205-1220. 

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