Exercise-induced muscle vasodilatation and genetic polymorphisms of alpha-adrenergic receptors, endothelial nitric oxide synthase and bradykinin receptor B2 in individuals without overt heart disease

Abstract

Purpose: Impaired peripheral vasodilatation has been associated with atherosclerosis and cardiovascular disease. The aim of this study was evaluate associations between common genetic polymorphisms of alpha-adrenergic receptors (ADRA1A, ADRA2A and ADRA2B), endothelial nitric oxide synthase (eNOS) and bradykin receptor B2 (BK2R) and exercise-induced muscle vasodilatation in men and women without established cardiovascular disease. Methods: We enrolled 766 (417 women and 349 men) individuals without established heart disease that had attended a check-up program at an University Hospital. The muscle vasodilation was studied with venous occlusion plethysmography and determined by the increase of forearm vascular conductance (forearm blood flow/mean arterial blood pressure) during 3-minute isometric handgrip exercise. Genotypes for the ADRA1A Arg347Cys (rs1048101), ADRA2A C1780T (rs553668), ADRA2B Del 301-303 (rs28365031), eNOS 786T/C (rs2070744), eNOS Glu298Asp (rs1799983) and BK2R (rs5810761) polymorphisms were assessed by polymerase chain reaction (PCR) followed by high resolution melting (HRM) analysis with the Rotor-Gene 6000(®) instrument. Laboratory and demographic data were collected for all participants. Statistical analysis was performed with linear mixed models for women and men. Results: The genotype frequencies were under Hardy-Weinberg equilibrium, except for the ADRA2B Del301-303 polymorphism. The ADRA2A C1780T polymorphism was significantly associated with forearm vascular conductance increase in men. Men with TT genotype have higher muscle vasodilatation than carriers of CT and CC genotypes (P = 0.035). The eNOS 786 T/C polymorphism was significantly associated with forearm vascular conductance increase in women. Women with CC genotype have higher muscle vasodilatation than carriers of TC and TT genotypes (P = 0.029). Conclusions: The polymorphisms ADRA2A C1780T and eNOS 786T/C influenced the exercise-induced muscle vasodilatation in this study. These findings suggest that genetic variants of alpha-adrenergic receptors and endothelial nitric oxide synthase may be important to regulation of vascular function in apparently healthy individuals and these responses may be gender-related.