Time-dependent adaptation in the hemodynamic response to hypoxia

Abstract

In rats, acute exposure to hypoxia causes a decrease in mean arterial pressure (MAP) caused by a predominance of hypoxic vasodilation over chemoreflex-induced vasoconstriction. We previously demonstrated that exposure to chronic intermittent hypoxia (CIH) impairs hypoxic vasodilation in isolated resistance arteries; therefore, we hypothesized that the acute systemic hemodynamic responses to hypoxia would be altered by exposure to CIH. To test this hypothesis, rats were exposed to CIH for 14 days. Heart rate (HR) and MAP were monitored by telemetry. On the first day of CIH exposure, acute episodes of hypoxia caused a decrease in MAP (-9+/-5 mmHg) and an increase in HR (+45+/-4 beats/min). On the 14th day of CIH exposure the depressor response was attenuated (-4+/-1mmHg; 44% of the day 1 response) and the tachycardia was enhanced (+68+/-2 beats/min; 151% of the day 1 response). The observed time-dependent modulation of the acute hemodynamic responses to hypoxia may reflect important changes in neurocirculatory regulation that contribute to CIH-induced hypertension.

Figure 1

On the first day of chronic intermittent hypoxia (CIH) exposure (left panel), hypoxia episodes caused decreases in mean arterial pressure (MAP) and increases in heart rate (HR) (filled circles). During the same sampling intervals, MAP and HR in normoxic control (NORM) rats remained stable (open circles). On the 14^th and final day of exposure (right panel), intermittent hypoxia episodes caused decreases in MAP that were smaller and increases in HR that were larger than those observed on the first day of exposure. During the same sampling intervals, MAP and HR in NORM rats remained stable. For each rat, we calculated a daily average of the 10-second binned values for HR and MAP during the 180 individual episodes of hypoxia in CIH rats and corresponding normoxic periods in NORM rats. Composite responses were determined by averaging each animal's mean value for each time point across all rats in a given experimental group.

Figure. 2

Maximal deviations from baseline in mean arterial pressure (MAP) and heart rate (HR) during episodes of hypoxia or corresponding normoxic periods in normoxic control (NORM) rats were determined for each animal and then averaged across all animals in each group to give a day-by-day assessment of peak hemodynamic responses. Over time, exposure to chronic intermittent hypoxia (CIH) blunted the depressor responses to individual intermittent hypoxia cycles that are typical in the rat (left panel), whereas heart rate responses were augmented (right panel). The filled bars show maximal deviations in MAP and HR in CIH rats, and the open bars show maximal deviations in MAP and HR measured during the same time frames in NORM rats. *P<0.10 for group by time interactions.

Figure 3

For each day of the experimental protocol, we computed an average mean arterial pressure (MAP) during the 12-hour light cycle and the 12-hour dark cycle for each rat in the chronic intermittent hypoxia (CIH) and normoxic control (NORM) group. Then, daily group mean values for each cycle were calculated. Day 0 values are the means obtained during a 5-day normoxic baseline period. Exposure to CIH produced increases in MAP above baseline that were evident during the dark cycle (top panel), when intermittent hypoxic cycles occurred, and also during the light cycle (bottom panel), when the animals were unperturbed. *P<0.05 vs. baseline value, # P<0.05 for CIH vs. NORM.

Figure 4

Exposure to chronic intermittent hypoxia (CIH) produced increases in heart rate above baseline that were evident during the dark cycle (top panel), when intermittent hypoxic cycles occurred, and also during the light cycle (bottom panel), when the animals were unperturbed. *P<0.05 vs. baseline value, # P<0.05 for CIH vs. NORM. Data points were computed as described in Figure 3.