The angiotensin-converting enzyme gene polymorphism and responses to angiotensins and bradykinin in the human forearm.
The deletion (D) allele of the angiotensin-converting enzyme (ACE) is associated with high ACE levels. Subjects homozygous for the D allele should therefore exhibit enhanced angiotensin I-induced vasoconstrictor responses and diminished bradykinin-induced vasodilator responses as compared with subjects homozygous for the insertion (I) allele. In eight II and eight DD normotensive male subjects, angiotensin I, bradykinin, and angiotensin II were infused in the forearm. Changes in forearm blood flow were registered with venous occlusion plethysmography. Blood was sampled to quantify angiotensin 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 in angiotensin I to II conversion, angiotensin H vasoconstriction, and bradykinin vasorelaxation were found. The ACE-inhibitor enalaprilate inhibited angiotensin I-induced vasoconstriction, but did not significantly affect bradykinin-induced vasodilation. The AT1-receptor antagonist losartan (3,000 ng/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 enhanced angiotensin I to II conversion rate or a difference in vascular reactivity. Possibly therefore, differences in angiotensin I to II conversion occur within the vascular wall only, at a site that does not readily equilibrate with blood plasma.
van Dijk
M A
MA
Department of Nephrology, Leiden University Medical Centre, The Netherlands. marjanvd@hotmail.com
Kroon
I
I
Kamper
A M
AM
Boomsma
F
F
Danser
A H
AH
Chang
P C
PC
D000328:Adult; D000368:Aged; D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D005542:Forearm / Q000098:blood supply*; D005838:Genotype; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000187:drug effects / Q000235:genetics*; D010991:Plethysmography; D011110:Polymorphism, Genetic; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D009599:Nitroprusside; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin