title: The Trp64Arg beta3-adrenergic receptor amino acid variant confers increased sensitivity to the pressor effects of noradrenaline in Sardinian subjects.
abstract: The beta(3)-adrenergic receptor (beta(3)AR) 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 beta(3)AR 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 beta(3)AR 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 beta(3)AR and eight with the Trp64Arg variant. The subjects each received, on two different days (randomized, double-blind fashion), a 4 h infusion of either noradrenaline (0.147 nmol.min(-1).kg(-1)) or Emagel (subjects had fasted for at least 12 h). The only available subject with a homozygous mutant Arg64Arg beta(3)AR was also studied. Blood pressure was measured every 10 min using a sphygmomanometer, and blood samples were taken every 30 min from the contralateral vein for biochemical determinations. After a 4 h noradrenaline infusion, significant increases in diastolic blood pressure (from 83+/-2 to 91+/-3 mmHg; P <0.01) and serum triacylglycerol levels (from 1.69+/-0.4 to 1.79+/-0.6 mmol/l; P <0.05) were observed compared with basal values in subjects with the Trp64Arg beta(3)AR variant, whereas subjects with the Trp64Trp beta(3)AR did not show any significant change over the infusion period. Glycaemia had increased significantly only at the end of the first 1 h of infusion in subjects with the Trp64Arg variant (from 5.0+/-0.1 to 5.8+/-0.3 mmol/l; P <0.05), with no significantly different behaviour compared with those subjects with the Trp64Trp beta(3)AR 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 beta(3)AR confers increased sensitivity to the pressure effect of noradrenaline. Moreover, this variant also influences blood triacylglycerol levels and, to a degree, glucose metabolism.
authors.affiliation: Servizio Diabetologia, Istituto di Clinica Medica, Dipartimento Struttura Clinica Medica e Patologia Medica, Viale S Pietro 8, 07100 Sassari, Italy.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Melis
authors.forename: Giannina
authors.initials: G
authors.lastname: Secchi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Brizzi
authors.forename: Cristiana
authors.initials: C
authors.lastname: Severino
authors.forename: Mario
authors.initials: M
authors.lastname: Maioli
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Tonolo
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics*; D014280:Triglycerides / Q000097:blood; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D022702:Receptors, Adrenergic, beta-3; D014280:Triglycerides; D014662:Vasoconstrictor Agents; D009638:Norepinephrine