Haemodynamic characterization of young normotensive men carrying the 825T-allele of the G-protein β3 subunit


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Abstract

A C825T polymorphism was recently identified in the gene for the G-protein β3 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 β-adrenoceptor antagonist, propranolol, and the α2-adrenoceptor agonist, α-methylnoradrenaline, and with regard to local venous vasoconstriction in the dorsal hand vein in situ following infusion of the α2-adrenoceptor agonist, azepexol. α2-Adrenoceptor agonists were chosen as vasoconstrictor drugs since α2-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 α-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 α2-adrenoceptors. However, this allele may be associated with elevated cardiac stroke volume.

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