Skip to main content
Log in

Polymorphic inhibition of human angiotensin I-converting enzyme by enalaprilat

  • Pharmacodynamics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Many individuals possess an allele of the angiotensin I-converting enzyme (ACE) gene, which contains an extra 287-kb fragment in intron 16 (Rigat et al. 1992). Although the functionality of this fragment is at present unclear, the absence (deletion, D) or presence (insertion, I) of this fragment appears to be related to both the amount and activity of circulating ACE. This paper reports the possible polymorphic response of ACE to the ACE inhibitor enalaprilat in 54 normal Chinese subjects that is independent of the I/D polymorphism. The kinetics of ACE inhibition with enalaprilat was studied in serum from 54 normal Chinese subjects. Enalaprilat appK i ranged between 0.46 and 2.16 nM. An antimode was observed at 1.4 nM. Four subjects could be characterized as being poor responders to enalaprilat.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Cambien F, Poirier O, Lecerf L, Evans A, Cambou J-P, Arveiler D, Luc G, Bard J-M, Bara L, Ricard S, Tiret L, Amouyel P, Alhenc-Gelas F, Soubrier F (1992) Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 359:641–4

    Google Scholar 

  • Friedland J, Silverstein E (1976) A sensitive fluorimetric assay for serum angiotensin-converting enzyme. Am J Clin Pathol 66:416–23

    Google Scholar 

  • Higashimori K, Zhao Y, Higaki J, Kamitani A, Katsuya T, Nakura J, Miki T, Mikami H, Ogihara T (1993) Association analysis of a polymorphism of the angiotensin converting enzyme gene with essential hypertension in the Japanese population. Biochem Biophys Res Commun 191:399–404

    Google Scholar 

  • Hubert C, Houot A-M, Corvol P, Soubrier F (1991) Structure of the angiotensin I-converting enzyme gene: two alternate promoters correspond to evolutionary steps of a duplicated gene. J Biol Chem 266:15377–15383

    Google Scholar 

  • Kaplan HR, Taylor DG, Olson SC, Andrews LK (1989) Quinapril — a preclinical review of the pharmacology, pharmacokinetics, and toxicology. Angiology 40:335–350

    Google Scholar 

  • Lee EJD (1994a) Population genetics of the angiotensin-converting enzyme in Chinese. Br J Clin Pharmacol 37:212–214

    Google Scholar 

  • Lee EJD (1994b) The angiotensin I-converting enzyme genetic polymorphism is associated with altered substrate affinity. Pharmacogenetics 4:101–103

    Google Scholar 

  • Morris BJ, Zee RYL, Ying LH, Griffiths LR (1993) Independent, marked associations of alleles of the insulin receptor and dipeptidyl carboxypeptidase genes with essential hypertension. Clin Sci 85:189–195

    Google Scholar 

  • Petrillo EW Jr, Ondetti MA (1982) Angiotensin-converting enzyme inhibitors: medicinal chemistry and biological actions. Med Res Rev 2:1–41

    Google Scholar 

  • Rigat B, Hubert C, Corvol P, Soubrier F (1992) PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme (DCP1) (dipeptidyl carboxypeptidase 1). Nucleic Acids Res 20:1433

    Google Scholar 

  • Shapiro R, Riordan JF (1984) Inhibition of angiotensin converting enzyme: mechanism and substrate dependence. Biochemistry 23:5225–5233

    Google Scholar 

  • Tiret L, Rigat B, Visvikis S, Breda C, Corvol P, Cambien F, Soubrier F (1992) Evidence, from combined segregation and linkage analysis, that the variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet 1:197–205

    Google Scholar 

  • Wei L, Alhenc-Gelas F, Corvol P, Clauser E (1991) The two homologous domains of human angiotensin I-converting enzyme are both catalytically active. J. Biol Chem 266:9002–9008

    Google Scholar 

  • Zee RYL, Lou Y-K, Griffiths LR, Morris BJ (1992) Association of a polymorphism of the angiotensin I-converting enzyme gene with essential hypertension. Biochem Biophys Res Commun 184:9–15

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, E.J.D. Polymorphic inhibition of human angiotensin I-converting enzyme by enalaprilat. Eur J Clin Pharmacol 49, 173–175 (1995). https://doi.org/10.1007/BF00192376

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00192376

Key words

Navigation