Circulating norepinephrine and cerebrovascular control in conscious humans.

BACKGROUND: Cerebral vasoconstriction without concurrent changes in systemic arterial blood pressure has been observed in both normal individuals and those with idiopathic orthostatic intolerance following several minutes of postural stress when circulating catecholamines are elevated. Therefore, we tested the hypothesis that alpha-adrenergic activation with and without elevated circulating norepinephrine (NE) directly affects cerebrovascular tone in healthy individuals. METHODS: Mean arterial pressure (MAP; tonometry) and cerebral blood flow velocity (MFV) in the middle cerebral artery (transcranial Doppler) were measured in seven healthy individuals during 15 min periods of saline and of 50 (low NE) and 100 (high NE) ng kg(-1) min(-1) infusions of NE. Following this, phentolamine (PHO) was administered to return MAP back to baseline while high NE infusion continued (high NE+PHO). Finally, NE infusion was stopped allowing the persistent effects of PHO to dominate. RESULTS: Circulating NE caused a dose-dependent increase in MAP (P<0.05). During combined high NE+PHO, blood pressure was initially reduced to baseline levels but then increased a second time (P<0.05) during the final approximately 5 min of this phase. MFV remained constant during both low NE and high NE. In contrast, the secondary increase in BP during the late high NE+PHO phase was associated with elevated MFV. Cerebral vascular resistance (CVR) increased during high NE but was reduced to baseline during both early and late portions of the combined high NE+PHO phase (i.e. despite the late-phase increase in blood pressure). CONCLUSIONS: The increase in CVR during NE infusion was explained by an autoregulatory response to the increased blood pressure and not an alpha-mediated constriction. However, PHO appeared to interfere with the normal autoregulatory response to increasing blood pressure.

Effects of pharmacological adrenergic and vagal modulation on fractal heart rate dynamics.

Breakdown of short-term fractal-like behaviour of HR indicates an increased risk for adverse cardiovascular events and mortality, but the pathophysiological background for altered fractal HR dynamics is not known. Our aim was to study the effects of pharmacological modulation of autonomic function on fractal correlation properties of heart rate (HR) variability in healthy subjects. Short-term fractal scaling exponent (alpha1) along with spectral components of HR variability were analysed during the following pharmacological interventions in healthy subjects: (i) noradrenaline (NE) infusion (n=22), (ii) NE infusion after phentolamine (PHE) (n=8), (iii) combined NE + adrenaline (EPI) infusion (n=12), (iv) vagal blockade with high dose of atropine (n=10), (v) and vagal activation by low dose of atropine (n=10). Then alpha1 decreased progressively during the incremental doses of NE (from 0.85 +/- 0.250 to 0.55 +/- 0.23, P<0.0001). NE also decreased the average HR (P<0.001) and increased the high frequency spectral power (P<0.001). Vagal blockade with atropine increased the alpha1 value (from 0.82 +/- 0.22 to 1.24 +/- 0.41, P<0.05). Combined NE + EPI infusion and vagal activation with a low dose atropine did not result in any changes in alpha1, and alpha-adrenergic blockade by PHE did not completely reverse the effects of NE on alpha1. Increased levels of circulating NE result in reduction of short-term correlation properties of HR dynamics. The results suggest that coactivation of cardiac vagal outflow at the time of high levels of a circulating sympathetic transmitter explains the breakdown of fractal-like behaviour of human HR dynamics.