The Trp64Arg β3-adrenergic receptor amino acid variant confers increased sensitivity to the pressor effects of noradrenaline in Sardinian subjects

Abstract

The β3-adrenergic receptor (β3AR) plays a critical role in lipid metabolism, and thus alterations in its function may be involved in the metabolic syndrome. Indeed, we have found previously that the Trp64Arg amino acid variant of the β3AR is associated with hypertension and higher serum triacylglycerol levels in the Sardinian population. The aim of the present study was to evaluate the effect of the Trp64Arg β3AR variant on the regulation of triacylglycerol levels and blood pressure during the exogenous infusion of noradrenaline. We studied groups of non-diabetic normotensive subjects: eight with the wild-type Trp64Trp β3AR and eight with the Trp64Arg variant. The subjects each received, on two different days (randomized, double-blind fashion), a 4h infusion of either noradrenaline (0.147nmol·min-1·kg-1) or Emagel (subjects had fasted for at least 12h). The only available subject with a homozygous mutant Arg64Arg β3AR was also studied. Blood pressure was measured every 10min using a sphygmomanometer, and blood samples were taken every 30min from the contralateral vein for biochemical determinations. After a 4h noradrenaline infusion, significant increases in diastolic blood pressure (from 83±2 to 91±3mmHg; P<0.01) and serum triacylglycerol levels (from 1.69±0.4 to 1.79±0.6mmol/l; P<0.05) were observed compared with basal values in subjects with the Trp64Arg β3AR variant, whereas subjects with the Trp64Trp β3AR did not show any significant change over the infusion period. Glycaemia had increased significantly only at the end of the first 1h of infusion in subjects with the Trp64Arg variant (from 5.0±0.1 to 5.8±0.3mmol/l; P<0.05), with no significantly different behaviour compared with those subjects with the Trp64Trp β3AR during the remaining infusion period. The effects of noradrenaline infusion were more marked in the subject with the Arg64Arg variant. In conclusion, our data indicate that the Trp64Arg amino acid variant of the β3AR confers increased sensitivity to the pressure effect of noradrenaline. Moreover, this variant also influences blood triacylglycerol levels and, to a degree, glucose metabolism.