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The first Sir George Pickering memorial lecture. Which inhibitors will give us true insight into what renin really does?

The first Sir George Pickering memorial lecture. Which inhibitors will give us true insight into what renin really does?

Journal of Hypertension 2(3): 223-230

The precise contribution of the renin-angiotensin system to the genesis of essential hypertension is difficult to discern from clinical studies with converting enzyme inhibitors because of their multiple pharmacological effects. Specific inhibitors of renin, appropriate for clinical investigation, would help to resolve this question. Four classes of compounds have been demonstrated to be renin inhibitors of high potency: specific antibodies, general peptide inhibitors of acid proteases, analogues of angiotensinogens, and peptides related to the amino-terminal sequence of prorenin. Of these, it is likely that angiotensinogen analogues will be the first to be applied in human studies. The minimal substrate for renin has the sequence: His-Pro-Phe-His-Leu-Leu-Val-Tyr. Variants of this sequence have yielded competitive inhibitors. Recently, remarkably active compounds have been synthesized by reducing the peptide bond cleaved by renin or by incorporating the amino acid statine, found in pepstatin. These compounds have now been shown to be effective in dogs, rats and monkeys, and, according to recent preliminary studies, in man.

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Accession: 044641404

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PMID: 6099385

DOI: 10.1097/00004872-198406000-00002

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