Clinical implications of the molecular biology of the renin-angiotensin system

Molecular cloning of the renin-angiotensin system (RAS) genes has supplied new tools for investigation for the pharmacologist, the physiologist and the geneticist concerned with blood pressure. The main questions regarding the RAS that can be addressed by molecular biology are: (1) How can new inhibitors of the RAS be designed? Molecular cloning of renin and angiotensin-converting enzyme and production of the corresponding recombinant protein are the basis for understanding the molecular mechanism of catalysis and for identifying residues corresponding to catalytic subsites. (2) Do local RASs exist and, if so, what is their physiological importance? Cloned genes of this system represent specific probes that can be used to identify the sites of transcription and to evaluate the degree of expression of the genes by measuring the level of their mRNA. (3) Is elevation of blood pressure in essential hypertension related to an abnormality in one of the RAS genes? Cloning of the different genes has allowed the detection of polymorphism at the nucleotide level, representing inter-individual variations of the sequences of the genes.