Exclusion of the ACE D/I Gene Polymorphism as a Determinant of Endothelial Dysfunction

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2001-02, Vol.37 (2), p.293-300
• Main Authors: Rossi, Gian Paolo, Taddei, Stefano, Virdis, Agostino, Ghiadoni, Lorenzo, Albertin, Giovanna, Favilla, Stefania, Sudano, Isabella, Pessina, Achille C., Salvetti, Antonio
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Adult; Alleles; Analysis of Variance; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; DNA - genetics; Dose-Response Relationship, Drug; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Female; Forearm - blood supply; Gene Deletion; Genotype; Humans; Hypertension - genetics; Hypertension - physiopathology; Male; Medical sciences; Middle Aged; Mutagenesis, Insertional; Nitroprusside - pharmacology; Peptidyl-Dipeptidase A - genetics; Polymorphism, Genetic; Regional Blood Flow - drug effects; Vasodilation - drug effects; Vasodilator Agents - pharmacology
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.37.2.293

A deletion/insertion (D/I) polymorphism within the ACE gene may increase the risk of cardiovascular events through still unknown mechanisms. The latter may involve increased angiotensin II–induced NO breakdown and/or reduced agonist-mediated NO release. We therefore investigated whether the D allele of the ACE gene affects endothelium-dependent vasodilatation in mild-to-moderate primary hypertensive patients and healthy normotensive subjects. We compared in a cross-sectional study the forearm blood flow response of the 3 D/I genotypes with 5 incrementally increasing doses of the endothelium-dependent vasodilator acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 μg · 100 mL · min) in 142 subjects103 mild-to-moderate uncomplicated primary hypertensives (49.3±9.1 years old, 152±11/99±5 mm Hg) and 39 normotensives (44.6±15.3 years old, 122±12/78±6 mm Hg). We also assessed the endothelium-independent vasodilatation in the forearm, as blood flow response to 3 incrementally increasing doses of sodium nitroprusside (1, 2, and 4 μg · 100 mL · min). The overall genotype distribution was II, n=10; ID, n=70; and DD, n=62. It did not differ significantly between primary hypertensives and normotensives. A significant blunting of endothelium-dependent vasodilatation in primary hypertensive patients compared with normotensive subjects (P