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(Hypertension. 2008;51:454.)
© 2008 American Heart Association, Inc.

Original Articles Part 2

Bradykinin Type 2 Receptor BE1 Genotype Influences Bradykinin-Dependent Vasodilation During Angiotensin-Converting Enzyme Inhibition

Gary P. Van Guilder; Mias Pretorius; James M. Luther; J. Brian Byrd; Kevin Hill; James V. Gainer; Nancy J. Brown

From the Division of Clinical Pharmacology (G.P.V.G., J.M.L., J.B.B., K.H., J.V.G., N.J.B.), Departments of Medicine and Pharmacology, and Department of Anesthesiology (M.P.), Vanderbilt University Medical Center, Nashville, Tenn; and the Veterans’ Affairs Medical Center (M.P., J.V.G.), Nashville, Tenn.

Correspondence to Nancy J. Brown, 23rd Ave at Pierce, 550 Robinson Research Building, Vanderbilt University Medical Center, Nashville, TN 37232-6602. E-mail nancy.j.brown{at}vanderbilt.edu

To test the hypothesis that the bradykinin receptor 2 (BDKRB2) BE1+9/–9 polymorphism affects vascular responses to bradykinin, we measured the effect of intra-arterial bradykinin on forearm blood flow and tissue-type plasminogen activator (t-PA) release in 89 normotensive, nonsmoking, white American subjects in whom degradation of bradykinin was blocked by enalaprilat. BE1 genotype frequencies were +9/+9:+9/–9:–9/–9=19:42:28. BE1 genotype was associated with systolic blood pressure (121.4±2.8, 113.8±1.8, and 110.6±1.8 mm Hg in +9/+9, +9/–9, and –9/–9 groups, respectively; P=0.007). In the absence of enalaprilat, bradykinin-stimulated forearm blood flow, forearm vascular resistance, and net t-PA release were similar among genotype groups. Enalaprilat increased basal forearm blood flow (P=0.002) and decreased basal forearm vascular resistance (P=0.01) without affecting blood pressure. Enalaprilat enhanced the effect of bradykinin on forearm blood flow, forearm vascular resistance, and t-PA release (all P<0.001). During enalaprilat, forearm blood flow was significantly lower and forearm vascular resistance was higher in response to bradykinin in the +9/+9 compared with +9/–9 and –9/–9 genotype groups (P=0.04 for both). t-PA release tended to be decreased in response to bradykinin in the +9/+9 group (P=0.08). When analyzed separately by gender, BE1 genotype was associated with bradykinin-stimulated t-PA release in angiotensin-converting enzyme inhibitor–treated men but not women (P=0.02 and P=0.77, respectively), after controlling for body mass index. There was no effect of BE1 genotype on responses to the bradykinin type 2 receptor–independent vasodilator methacholine during enalaprilat. In conclusion, the BDKRB2 BE1 polymorphism influences bradykinin type 2 receptor–mediated vasodilation during angiotensin-converting enzyme inhibition.

Key Words: bradykinin • genotype • vasodilation • angiotensin-converting enzyme • plasminogen activators

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