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

• DOI: 10.1161/hypertensionaha.107.102574
• Publication Date: 2008-01-08T01:53:35Z
• Authors: Gary P. Van Guilder; Mias Pretorius; James M. Luther; J. Brian Byrd; Kevin Hill; James V. Gainer; Nancy J. Brown
• Keywords: Adult; Male; Nitroprusside; Genotype; Receptor, Bradykinin B2; Vasodilator Agents; 610; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Bradykinin; Cardiovascular System; Injections; 03 medical and health sciences; Sex Factors; 0302 clinical medicine; Genetic; Vascular; Bradykinin B2; Humans; Endothelium; Polymorphism; Circulatory and Respiratory Physiology; Methacholine Chloride; Polymorphism, Genetic; Intra-Arterial; Drug Synergism; 3. Good health; Vasodilation; Forearm; Injections, Intra-Arterial; Regional Blood Flow; Enalaprilat; Tissue Plasminogen Activator; Vascular Resistance; Female; Endothelium, Vascular; Receptor

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.