Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mean arterial blood pressure (MAP) was 100 +/- 4 mmHg in a group (n = 3) of conscious sodium-deficient dogs. A 3-day infusion of the renin inhibitor isovaleryl -His-Pro-Phe-His-Sta-Leu-Phe-NH2 (SCRIP) lowered MAP to an average of 79 +/- 4 mmHg. Termination of the infusion resulted in a prompt rise in MAP to 100 +/- 5 mmHg but plasma renin activity (PRA), which was 22 +/- 2 ng angiotensin (Ang) l/ml per h before the infusion, recovered only to 5 +/- 1 ng Ang l/ml per h during the same time (4 h after infusion). In other experiments in sodium-deficient dogs, a direct comparison was made between inhibition of PRA and the reduction of blood pressure. Over the dose range 0.1-2 micrograms/kg per min, PRA was inhibited in a dose-related manner, but MAP was not reduced. At dose levels beginning an order of magnitude higher (e.g. 20-160 g/kg per min), PRA was completely inhibited and there was a dose-related fall in MAP. These data suggest that there is no correlation between inhibition of PRA and the reduction in blood pressure in chronically sodium-deficient dogs. In other studies comparing renin inhibition with angiotensin converting enzyme (ACE) inhibition, there was evidence for greater efficacy of ACE inhibition in conscious sodium-deficient dogs, but no evidence of any difference in one-kidney, one clip hypertensive dogs.
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PMID:Characteristics of the blood pressure lowering action of renin inhibition and comparison with angiotensin converting enzyme inhibition. 266 14

Dipeptide and tripeptide derivatives containing a statine residue were synthesized as inhibitors of human renin. ES-305, bis[(1-naphthyl)methyl]acetyl(BNMA)-histidyl-statine 2(S)-methylbutylamide was found to be a highly potent inhibitor of human renin with a Ki value of 1.7 X 10(-9) M. Dipeptide derivatives with the BNMA group at the N-terminal (BNMA-Val-Sta-isoleucinol [ES-313], BNMA-Leu-Sta-isoleucinol [ES-316], and BNMA-Nle-Sta-isoleucinol [ES-317]) had potencies against human renin that were similar to the potency of ES-305. All these dipeptide derivatives competitively inhibited human renin. The inhibitors were also potent against monkey renin but were less effective against renins from pig, goat, dog, rabbit, and rat. ES-305 had little effect on cathepsin D and pepsin at the concentration of 10(-5) M. The other derivatives showed detectable inhibition of cathepsin D (IC50, 10(-6) - 10(-7) M) and pepsin (10(-5) - 10(-6) M). All the compounds had little or no effect on trypsin, chymotrypsin, angiotensin converting enzyme, and urinary kallikrein at the concentration of 10(-5) M. Our results indicate that ES-305 is a highly potent and specific inhibitor of human renin. This compound is superior to other, previously described statine-containing renin inhibitors with respect to molecular size and enzyme specificity.
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PMID:Statine-containing dipeptide and tripeptide inhibitors of human renin. 308 74