Pierre Corvol

Molecular biology of the angiotensin I converting enzyme

The discovery of orally active angiotensin converting enzyme (ACE) inhibitors is one of the major therapeutic advances of the last decade. However, the structure of this enzyme was not determined until recently. Molecular cloning of the enzyme has now opened up new and fascinating areas of research with important clinical implications.

The Renin Gene

The renin angiotensin system plays a major role in the control of blood pressure and electrolyte balance. It is implicated in essential hypertension, and therefore, its inhibition constitutes the major therapeutic advance in the treatment of cardiovascular disease of these last few years. The structure and organization of the renin gene have recently been elucidated, and the advances concerning this gene in mouse and humans will be reviewed in this chapter.

Direct Radioimmunoassay for Rat High Molecular Weight Kininogen

A direct radioimmunoassay (RIA) for rat high molecular weight kininogen (HMW Kg) was developed that enabled us to detect 71 fmol/ml of HMW Kg. The antibodies did not crossreact in the RIA with up to 5 nmol of purified rat alpha 1 cysteine proteinase inhibitor (T-kininogen). When various quantities of pure HMW Kg were either quantified by the RIA or by the measurement of kinin contents determined after trypsin hydrolysis, identical values were obtained by both methods. This RIA allowed the measurement of HMW Kg in 0.015 to 1 microliter of rat plasma. HMW Kg levels in plasma of Wistar rats and in Brown Norway rats of the Orlean Strain (BN/Orl) were 1.52 +/- 0.05 (n = 6) and 2.050 +/- 0.015 (n = 8) nmol/ml respectively. In the Brown Norway rats of the Katholiek strain (BN/Kat) that are considered to be deficient in HMW Kg, immunoreactive HMW Kg levels were less than 2% of those of the BN/Orl rats. These results confirm that the BN/Kat animals have a molecular defect in HMW Kg.