Showing papers by "Suzanne Oparil published in 1974"

The renin-angiotensin system (first of two parts).

Abstract: TIGERSTEDT and Bergman established a role for the kidney in blood-pressure regulation at the close of the 19th century. In a classic experiment, they produced hypertension in dogs by injecting a cr...

Effects of pH and Enzyme Inhibitors on Apparent Generation of Angiotensin I in Human Plasma.

Abstract: Apparent generation.of angiotensin I (AI) in human plasma depends on choice of angiotensinase and converting enzyme inhibitors, pH of incubation, and unknown factors in individual plasma samples. The shape of pH curves for AI generation in human plasma varies with choice of enzyme inhibitors, suggesting that such curves reflect a titration of inhibitor effectiveness as well as a measure of renin activity. AI is generated from anephric plasma incubated at acid but not at neutral pH, suggesting the participation of acid proteases. Lowering the pH of incubation of patient samples from 7.4 to 5.5 does not cause an invariable increase in AI generation. The effects of acidifying plasma on AI production vary greatly from sample to sample, and this variabiltiy should be taken into account when measurements of plasma renin acitvity are carried out under unphysiologic conditions.

Structural requirements for substrates and inhibitors of angiotensin I-converting enzyme in vivo and vitro.

Abstract: The mechanism of action of peptide inhibitors on angiotensin I-converting enzyme (Al-converting enzyme) was studied in relation to the substrate requirements of the enzyme in vivo in the dog lung and in vitro in plasma. 1- d -Asp-8-Ile-AI prepared by the solid-phase technique was compared with the known peptide inhibitors of Al-converting enzyme. BPP5a (Pyr-Lys-Trp-Ala-Pro) and SQ 20881 (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro)125I-1- d -Asp-8-Ile-AI was evaluated for susceptibility to cleavage by the Al-converting enzyme. In vitro and in vivo, 125I-1- d -Asp-8-Ile-AI or BPP5a in 50,000-fold molar excess produced only a slight delay in conversion of 1251-AI to 125I-angiotension II (AII); SQ 20881 blocked conversion completely. In vivo, l- d -Asp-8-Ile-AI or BPP5a injected into the pulmonary circulation in 250-fold molar excess (250 nmole/kg) did not cause a diminution in the pressor response to AI administered 30 seconds later; SQ 20881 blocked the pressor response to Al for 60-90 minutes. 1- d -Asp-8-Ile-AI was a poor substrate for converting enzyme, since 125I-1- d -Asp-8-Ile-AI was not converted to 125I-1- d -Asp-8-Ile-AII, and unlabeled 1- d -Asp-8-Ile-AI did not block the pressor response to exogenous AII. 125I-1- d -Asp-8-lle-AI was stable in plasma and in the pulmonary circulation The results suggest that since 1- d -Asp-8-Ile-AI is neither a substrate nor a blocker, substitution of the aliphatic residue Ile in the 8 position of AI may prevent binding to an active site in the AI-converting enzyme.