期刊
HYPERTENSION
卷 51, 期 2, 页码 454-459出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.107.102574
关键词
bradykinin; genotype; vasodilation; angiotensin-converting enzyme; plasminogen activators
资金
- NCRR NIH HHS [M01 RR000095-46, M01 RR000095, M01RR000095] Funding Source: Medline
- NHLBI NIH HHS [R01 HL065193-07, R01 HL065193-06, R01 HL085740, R01 HL079184-03, R01 HL065193, R01 HL060906, R01 HL060906-08, HL065193, HL060906, T32 HL076133, R01 HL065193-05, R01 HL079184-01, R01 HL079184-02, HL076133, R01 HL065193-08A2, R01 HL079184-04, R01 HL085740-01, R01 HL079184] Funding Source: Medline
- NIGMS NIH HHS [R01 GM097569, T32 GM97569] Funding Source: Medline
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 oth). 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.
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