Is there diurnal variation of the vestibulosympathetic reflex: implications for orthostatic hypotension

Incidences of adverse cardiac events and orthostatic hypotension are associated with diurnal variations. The primary purpose of the present study was to determine if the vestibulosympathetic reflex (VSR) follows a diurnal variation in humans. We hypothesized that the VSR would be attenuated at night based on the relation between melatonin and the VSR. Arterial blood pressure, heart rate, calf blood flow, and muscle sympathetic nerve activity (MSNA) were measured in nine healthy subjects (28 ± 1 yr, 5 men and 4 women) at rest and during head-down rotation. Each subject was tested during the day at 11:34 ± 13 and again at night 22:10 ± 5. MSNA was significantly decreased at night compared with day (8 ± 1 vs. 11 ± 2 bursts/min, respectively, P < 0.02). Heart rate and arterial blood pressure at rest were significantly increased at night compared with day (heart rate: 70 ± 4 vs. 66 ± 4 beats/min and mean arterial blood pressure: 91 ± 2 vs. 87 ± 1 mmHg, respectively). MSNA and hemodynamic responses to head-down rotation were not significantly altered at night compared with day (changes of 3 ± 1 bursts/min and 25 ± 6% for MSNA and calf blood flow, respectively). The data indicate that MSNA at rest decreases during the late evening hours and exhibits a diurnal variation, whereas the VSR does not. In summary, diurnal variation of orthostatic hypotension in humans does not appear to be associated with changes in the VSR and MSNA at rest.

Inhibition of prostaglandin synthesis does not alter the decrease in pre-capillary resistance in the human calf in response to small cumulative increases in venous congestion

The decrease in pre-capillary resistance in the human calf during gradual cumulative increases in venous congestion pressure has been proposed to represent vasodilator signalling between the venous and arterial microcirculations. The present study investigated whether prostaglandins are involved in this local flow regulation by measuring calf blood flow and microvascular filtration capacity using strain gauge plethysmography in young male subjects before (baseline) and after taking either ibuprofen, an inhibitor of prostaglandin synthesis (1600 mg over 2 days), or placebo. At baseline, inflation of a thigh cuff to 50 mmHg in steps of 10 mmHg, each held for 5 min, did not decrease arterial inflow, confirming a reduction of pre-capillary resistance. Ibuprofen reduced resting calf blood flow by 35% (P<0.001), but flow at a Pcuff (cuff pressure) of 50 mmHg was 97% of this value, i.e. pre-capillary resistance had decreased to the same extent as before inhibition of prostaglandin synthesis. Ibuprofen also reduced microvascular filtration capacity (2.98±1.20 compared with 3.71±0.89 ml·min−1·100 ml−1·mmHg−1×10−3; P<0.05), probably due to a combination of reduced arterial inflow and lower venous pressure (8.5±5.2 compared with 12.6±2.8 mmHg; P<0.05) that moderated capillary hydrostatic pressure to override direct effects of inhibition of prostaglandin synthesis on permeability. Placebo was without effect on any measurement. It is unlikely therefore that prostaglandin-mediated vasodilator signals, which have been demonstrated between paired veins and arteries, are important in local vasodilation in response to venous congestion.