Haemodynamic characterization of young normotensive men carrying the 825T-allele of the G-protein beta3 subunit.
A C825T polymorphism was recently identified in the gene for the G-protein beta3 subunit, the T-allele being associated with hypertension. To better understand the underlying pathophysiological mechanisms, we compared the haemodynamics of young healthy males with and without the T-allele. In three studies, subjects were investigated with regard to cardiac and vascular function at rest and following intravenous administration of the beta-adrenoceptor antagonist, propranolol, and the alpha2-adrenoceptor agonist, alpha-methylnoradrenaline, and with regard to local venous vasoconstriction in the dorsal hand vein in situ following infusion of the alpha2-adrenoceptor agonist, azepexol. alpha2-Adrenoceptor agonists were chosen as vasoconstrictor drugs since alpha2-adrenoceptors couple to pertussis toxin (PTX)-sensitive G-proteins and since in-vitro studies have demonstrated enhanced signal transduction of PTX-dependent pathways in the presence of the T-allele. Total peripheral resistance was determined as a parameter of vasoconstrictor tone and heart rate, stroke volume and systolic time intervals for cardiac function. T-allele carriers had a significantly elevated stroke volume and lower total peripheral resistance at baseline. After propranolol, their fall in stroke volume was significantly greater. During alpha-methylnoradrenaline infusion, elevation of total peripheral resistance was not increased relative to controls. Similarly, the constriction response of the dorsal hand vein to azepexol was not different. Our study does not support the idea of increased vasoconstrictor tone in T-allele carriers either at rest or during stimulation of alpha2-adrenoceptors. However, this allele may be associated with elevated cardiac stroke volume.
Schäfers
R F
RF
Department of Medicine, University of Essen, Essen, Germany. rafael.schaefers@uni-essen.de
Nürnberger
J
J
Rütz
A
A
Siffert
W
W
Wenzel
R R
RR
Mitchell
A
A
Philipp
T
T
Michel
M C
MC
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000235:genetics*; D006334:Heart Function Tests; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008771:Nordefrin / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001381:Azepines; D011943:Receptors, Adrenergic, beta; D014662:Vasoconstrictor Agents; D011433:Propranolol; C015603:azepexole; D020962:Heterotrimeric GTP-Binding Proteins; D008771:Nordefrin