Angiotensin-Converting Enzyme and Genetic Hypertension: Cloning of Rat cDNAs and Characterization of the Enzyme

Abstract

Using genetic mapping approaches, a gene on chromosome 10, Bpl, has been identified in the stroke-prone spontaneously hypertensive rat (SHRSP) in the same region that contains the gene for angiotensin converting enzyme (ACE). Since ACE plays an important role in blood pressure regulation, the ACE gene is a leading candidate for Bpl. To examine the possibility that a structural abnormality of ACE exists in the SHRSP, we cloned and characterized the cDNAs for the Wistar-Kyoto rat (WKY) and SHRSP ACE. Both cDNAs encode a single polypeptide of 1,313 amino acid residues with an estimated molecular weight of 150.9 KDa. Five nucleotide differences were identified between the WKY and the SHRSP ACE cDNAs. One of these differences resulted in an amino acid substitution (Lys-207 in the WKY to Arg-207 in the SHRSP). But the enzymatic properties of partially purified ACE from the two strains were similar. Thus the data suggest that an alteration in the primary structure of rat ACE does not contribute to the hypertension in the SHRSP.