Small peptide analogues representing the C-terminal portion of angiotensin I sequence were designed as inhibitors of human renin. Among synthesized compounds, benzyloxycarbonyl (-"Z")-(1-naphthyl)Ala-His-leucinal (ES-188), Z-(1-naphthyl)Ala-His-statine ethyl ester (ES-226), and Z-(1-naphthyl)Ala-His-statine 2-methylbutylamide (ES-254) markedly inhibited human and primate renins (inhibitory concentration, 50% [IC50], near 10(-7) M). These peptide analogues inhibited rabbit renin with one or two orders of magnitude less potency. They were very weak inhibitors of renins from pig, goat, dog, and rat. ES-188 had no discernible effect on cathepsin D, pepsin, or human angiotensin-converting enzyme at the concentration of 10(-4)M. ES-226 had little effect on the three enzymes at the concentration of 10(-5)M; however, ES-254 had a considerable inhibitory effect on cathepsin D (IC50 of 1.4 X 10(-5)M), pepsin (IC50 of 4.2 X 10(-5)M), and human angiotensin-converting enzyme (IC50 of 7.1 X 10(-6)M). Our results indicate that 1-naphthylalanine-containing tripeptide analogues are highly potent human renin inhibitors.

Angiotensin I↗

PubMedDate not supplied

Nucleic DNA and RNA in cardiac muscle cell of experimental myocardial infarct.

Myocardial infarction was produced in dogs, and the changes in nucleic acid synthetic activity were investigated quantitatively by microspectrophotometer in the myocardial cells as time progressed. DNA value, immediately after infarction, was greatly increased in comparison to that of the control group. At two weeks after infarction the value had increased to the highest level. After this point the value decreased, and, in 12 weeks, the mean value was back to the control level. Changes in RNA followed a pattern similar to DNA changes. The mechanism of the repair process of myocardial infarction was investigated.

Animals↗

PubMedDate not supplied

Absorption rates of L-tryptophan, L-methionine, and L-methionyl-L-tryptophan by rat intestine in vitro and in vivo.

The absorption rates of L-tryptophan, L-methionine, and L-methionyl-L-tryptophan were determined by both the everted sac and the tied loop method with rat intestines. In the everted sac method, high concentrations of L-tryptophan or L-methionyl-L-tryptophan caused anomalous inhibition of absorption of L-tryptophan and L-methionine. The rates of absorption of both L-tryptophan and L-methionyl-L-tryptophan decreased markedly at concentrations higher than 2-3mM. This inhibition was not observed in the tied loop method. Chromatographic, electrophoretic, and microscopic studies suggested that such decreases in absorption rate were caused mainly by decomposition of L-tryptophan to some basic incubation products containing tryptamine with consequent damage to the mucosal surface of everted sacs during long-term incubation. In the tied loop method, L-methionyl-L-tryptophan was absorbed more rapidly than either of the constituent amino acids in equimolar mixture.

Animals↗