Enhanced Pressor Response to Angiotensin I in Normotensive Men With the Deletion Genotype (DD) for Angiotensin-Converting Enzyme

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 25; no. 6; pp. 1266 - 1269
• Main Authors: Ueda, Shinichiro, Elliott, Henry L, Morton, James J, Connell, John
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01-06-1995; Hagerstown, MD Lippincott
• Subjects: Adult; Aldosterone - blood; Angiotensin I - pharmacology; Angiotensin II - blood; Angiotensin II - pharmacology; Base Sequence; Biological and medical sciences; Blood Pressure - drug effects; Fundamental and applied biological sciences. Psychology; Genotype; Hemodynamics. Rheology; Humans; Male; Molecular Sequence Data; Peptidyl-Dipeptidase A - genetics; Renin - blood; Vertebrates: cardiovascular system; Chromosomal aberration; Human; Genetic inheritance; Enzyme; Angiotensin I; Peptide hormone; Genotype; Male; Renin angiotensin system; Peptidyl-dipeptidase A; Deletion; Abnormal chromosome; Hydrolases; Peptidyl-dipeptidases; Arterial pressure; Circulatory system; Hemodynamics; Proteinases; Polymorphism
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.25.6.1266

The insertion (I)/deletion (D) polymorphism of the human angiotensin-converting enzyme gene has emerged as a genetic risk factor for ischemic heart disease. However, the functional consequences of this polymorphism in humans are not known. Ten normotensive men with the DD genotype and 10 with the II genotype participated in a study in which pressor responses to stepwise infusions of incremental doses of angiotensin I (Ang I) and Ang II and Ang II production during Ang I infusion were measured. Pressor responses were expressed as PD20, which reflects the angiotensin dose required to raise mean blood pressure by 20 mm Hg. The PD20 for Ang I in subjects with the DD genotype was significantly lower than that in II genotype subjects (8.8 versus 14.8 ng/kg per minute, P = .0091), whereas the PD20 for Ang II between the two groups did not differ significantly. The ratio of PD (20) for Ang I and Ang II in DD subjects was significantly lower than that in II subjects (0.85 versus 0.96, P = .0452), and the venous levels of Ang II during Ang I infusion in DD subjects were significantly higher than those in II subjects (P < .01). Our study has shown increased pressor responsiveness to Ang I, probably as a consequence of the generation of increased Ang II levels, in subjects homozygous for the DD allele of the angiotensin-converting enzyme gene. This result may be relevant to the reported adverse cardiovascular risk conferred by the D allele, as it provides a mechanistic rationale for the association between this polymorphism and cardiovascular disease. (Hypertension. 1995;25:1266-1269.)