Effects of common polymorphisms in the α1A-, α2B-, β1- and β2-adrenoreceptors on haemodynamic responses to adrenaline

Common naturally occurring polymorphisms have been identified in the coding regions of the α_1A-, α_2B-, β₁- and β₂-adrenoceptor (AR) genes [α_1A-AR R492C, α_2B-AR insertion/deletion (I/D), β₁-AR R389G, β₂-AR G16R and β₂-AR Q27E] and are associated with modified in vivo and in vitro functionality. We tested their possible effects on the haemodynamic responses to intravenous adrenaline (20, 40, 80 and 160ng/kg of body weight per min; 5min for each infusion rate) before and after β-blockade (propranolol) in 16 young healthy men. We monitored changes in heart rate, blood pressure (BP), ECG, coronary flow velocity and plasma adrenaline and noradrenaline. The Cys/Cys (CC) genotype of the α_1A-AR R492C polymorphism was associated with a longer ECG PR interval before and during the adrenaline infusions. The deletion/deletion (D/D) genotype of the α_2B-AR I/D polymorphism was associated with blunted coronary blood flow increases during the adrenaline infusion before β-blockade. The β₁-AR R389G polymorphism was not associated with modified responses to infused adrenaline. Subjects carrying the Gly/Gly (GG) genotype of the β₂-AR G16R polymorphism demonstrated increases in diastolic BP upon adrenaline infusion, whereas diastolic BP was decreased in the other genotype groups. These results suggest that, upon acute adrenaline infusion, the α_2B-AR D/D genotype confers increased vasoconstriction and that the β₂-AR GG genotype confers reduced vasodilatation.