The angiotensin-converting enzyme gene polymorphism and responses to angiotensins and bradykinin in the human forearm

deletion (D) allele of the angiotensin-converting enzyme (ACE) is associate d with high ACE levels. Subjects homozygous for the D allele should therefo re exhibit enhanced angiotensin I-induced vasoconstrictor responses and dim inished bradykinin-induced vasodilator responses as compared with subjects homozygous for the insertion (I) allele. In eight II and eight DD normotens ive male subjects, angiotensin I, bradykinin, and angiotensin II were infus ed in the forearm. Changes in forearm blood flow were registered with venou s occlusion plethysmography. Blood was sampled to quantify aneiotensin I to II conversion. Plasma ACE levels were 60%; higher, and DD subjects showed an enhanced response to angiotensin I infusion (p < 0.05). No differences i n angiotensin I to II conversion, angiotensin II vasoconstriction. and brad yhinin vasorelaxation were found. The ACE-inhibitor enalaprilate inhibited angiotensin I-induced vasoconstriction, but did not significantly affect br adykinin-induced vasodilation. The AT,receptor antagonist losartan (3,000 n g/kg/min) inhibited angiotensin II-induced vasoconstriction. In conclusion, subjects with the DD genotype display an enhanced vasoconstrictor response to angiotensin I, which cannot be explained on the basis of a similarly en hanced angiotensin I to II conversion rate or a difference in vascular reac tivity. Possibly therefore, differences in angiotensin I to II conversion o ccur within the vascular wall only, at a site that does not readily equilib rate with blood plasma.