Effects of common polymorphisms in the alpha1A-, alpha2B-, beta1- and beta2-adrenoreceptors on haemodynamic responses to adrenaline.

Common naturally occurring polymorphisms have been identified in the coding regions of the alpha(1A)-, alpha(2B)-, beta(1)- and beta(2)-adrenoceptor (AR) genes [alpha(1A)-AR R492C, alpha(2B)-AR insertion/deletion (I/D), beta(1)-AR R389G, beta(2)-AR G16R and beta(2)-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 160 ng/kg of body weight per min; 5 min for each infusion rate) before and after beta-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 alpha(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 alpha(2B)-AR I/D polymorphism was associated with blunted coronary blood flow increases during the adrenaline infusion before beta-blockade. The beta(1)-AR R389G polymorphism was not associated with modified responses to infused adrenaline. Subjects carrying the Gly/Gly (GG) genotype of the beta(2)-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 alpha(2B)-AR D/D genotype confers increased vasoconstriction and that the beta(2)-AR GG genotype confers reduced vasodilatation.