Human renin protein and gene structures: present and future targets for renin blockade in treatment of hypertension.
The cloning of the gene for human renin has permitted remarkable advances to be made in understanding the structure of this aspartyl protease. From computer models and the determination of the actual co-ordinates of expressed recombinant human renin at 3 nm, a considerable amount of information has emerged concerning the molecular mechanism of renin activity, thus permitting the logical design and analysis of renin inhibitors suitable for use in antihypertensive medication. In addition, many of the properties of renin can now be explained in molecular terms, including the species specificity of its reaction with angiotensinogen. From the production of renin inhibitors, the next avenue of research is likely to be the design of drugs that will reduce the activity of the human renin gene and thereby curtail renin production. This may involve a 'new pharmacology' based on transacting factors. Thus cloning of the renin gene has led to elucidation of the tertiary structure of human renin for inhibitor design, and will similarly permit studies of gene-regulatory factors that may be future targets for blockade of the renin system in antihypertensive therapy.