Left ventricular ejection time: a potential determinant of pulse wave velocity in young, healthy males.

OBJECTIVE: Pulse wave velocity (PWV) is a classic marker of vascular stiffness. Recent studies showed that heart rate is an important determinant of PWV. The purpose of this study was to evaluate the role of myocardial function in determining PWV under resting conditions and under adrenergic stimulation. DESIGN AND METHODS: Hemodynamic parameters were investigated under resting conditions in 102 young, healthy males and under stimulation of either beta- or alpha(2)-adrenoceptors in six young, healthy males. PWV was determined from pressure tracing over the carotid and femoral artery. Central hemodynamics were assessed by impedance cardiography and systolic time intervals. Simple (r) and multiple (beta) regression analyses were used to assess the relationships between PWV and hemodynamic parameters. RESULTS: Under resting conditions, PWV was correlated to age (beta = 0.259, P = 0.0052), diastolic blood pressure (beta = 0.279, P = 0.0072) and left ventricular ejection time (beta = -0.314, P = 0.0277). Under alpha(2)-adrenergic stimulation PWV was only correlated to diastolic blood pressure (DBP) (beta = 0.806, P = 0.0020). Under beta-adrenergic stimulation PWV was only correlated to left ventricular ejection time index (r = -0.52, P = 0.0325). CONCLUSIONS: Left ventricular ejection time may be an important determinant of pulse wave velocity under resting and adrenergic conditions in young, healthy males. Further studies are needed to evaluate this relationship in other populations including females and patients with cardiovascular disease.

Metabolic and haemodynamic effects of oral glucose loading in young healthy men carrying the 825T-allele of the G protein beta3 subunit.

BACKGROUND: A C825T polymorphism was recently identified in the gene encoding the beta3 subunit of heterotrimeric G-proteins (GNB3). The T-allele is significantly associated with essential hypertension and obesity. In order to further explore a possible pathogenetic link between the T-allele and impaired glucose tolerance we studied metabolic and haemodynamic responses to oral glucose loading in young, healthy subjects with and without the 825T-allele. METHODS: Twelve subjects with and 10 without the 825T-allele were investigated at rest and following glucose ingestion (75 g). Blood glucose, serum insulin and haemodynamics were determined prior to and over 2 hours following glucose ingestion. We non-invasively measured stroke volume (SV, by impedance-cardiography), blood pressure (BP), heart rate (HR), and systolic-time-intervals. Cardiac output (CO) was calculated from HR and SV. Total peripheral resistance was calculated from CO and BP. Metabolic and haemodynamic changes were quantified by maximal responses and by calculation of areas under the concentration time profile (AUC). Significances of differences between subjects with and without the T-allele were determined by unpaired two-tailed t-tests. A p < 0.05 was considered statistically significant. RESULTS: Metabolic and haemodynamic parameters at baseline were very similar between both groups. The presence of the T-allele did not alter the response of any metabolic or haemodynamic parameter to glucose loading. CONCLUSIONS: In conclusion, this study does not support the hypothesis that the C825T polymorphism may serve as a genetic marker of early impaired glucose tolerance.

Effect of the C825T polymorphism of the G protein beta 3 subunit on the systolic blood pressure-lowering effect of clonidine in young, healthy male subjects.

The T allele of the C825T polymorphism in the gene encoding the G-protein beta 3 subunit (GNB3) is associated with hypertension. An enhanced signal transduction in response to alpha(2)-adrenergic receptor stimulation has been shown in carriers of the T allele in vitro. We hypothesized that T allele carriers would show an enhanced antihypertensive response to stimulation of central alpha(2)-adrenergic receptors by clonidine. We compared the response to intravenous clonidine in 30 young, healthy male subjects with and without the T allele (15 CC, 10 CT, and 5 TT). Clonidine lowered blood pressure and total peripheral resistance, lengthened the duration of electromechanical systole (QS(2)c), and slowed down pulse wave velocity. Carriers of the T allele showed significantly greater reductions in systolic blood pressure (P =.009; mean change +/- SEM: CC, -8.9 +/- 0.5; CT and TT, -10.6 +/- 0.4) and total peripheral resistance (P <.0001; mean change +/- SEM: CC, 40 +/- 17; CT and TT, -48 +/- 14) and more marked lengthening of QS(2)c (P =.002; mean change +/- SEM: CC, 2.2 +/- 0.5; CT and TT, 4.7 +/- 0.6) and slowing of pulse wave velocity (P =.012; mean change +/- SEM: CC, -0.25 +/- 0.02; CT and TT, -0.33 +/- 0.03). The results of this study suggest that the 825T allele may be a relevant pharmacogenetic marker in the use of centrally acting sympatholytic drugs.