Haemodynamic characterization of young normotensive men carrying the 825T-allele of the G-protein beta 3 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 u nderstand the underlying pathophysiological mechanisms, we compared the hae modynamics of young healthy males with and without the T-allele. In three s tudies, subjects were investigated with regard to cardiac and vascular func tion at rest and following intravenous administration of the beta -adrenoce ptor antagonist, propranolol, and the alpha (2)-adrenoceptor agonist, alpha -methylnoradrenaline, and with regard to local venous vasoconstriction in the dorsal hand vein in situ following infusion of the alpha (2)-adrenocept or agonist, azepexol. alpha (2)-Adrenoceptor agonists were chosen as vasoco nstrictor drugs since alpha (2)-adrenoceptors couple to pertussis toxin (PT X)-sensitive G-proteins and since in-vitro studies have demonstrated enhanc ed signal transduction of PTX-dependent pathways in the presence of the T-a llele. Total peripheral resistance was determined as a parameter of vasocon strictor tone and heart rate, stroke volume and systolic time intervals for cardiac function. T-allele carriers had a significantly elevated stroke vo lume and lower total peripheral resistance at baseline. After propranolol, their fall in stroke volume was significantly greater. During alpha -methyi noradrenaline infusion, elevation of total peripheral resistance was not in creased relative to controls. Similarly, the constriction response of the d orsal hand vein to azepexol was not different. Our study does not support t he idea of increased vasoconstrictor tone in T-allele carriers either at re st or during stimulation Of a(2)-adrenoceptors. However, this allele may be associated with elevated cardiac stroke volume. Pharmacogenetics 11:461-47 0 (C) 2001 Lippincott Williams & Wilkins.