Resetting of the sympathetic baroreflex is associated with the onset of hypertension during chronic intermittent hypoxia

Abstract

Chronic intermittent hypoxia (CIH) is a model of arterial hypoxemia that accompanies sleep apnea and increases resting arterial pressure (AP). We examined the effects of 7 days of exposure to CIH on arterial baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate (HR) in rats. Sprague-Dawley rats (15±2 weeks old) were exposed to CIH (9% oxygen for 3 min every 10 min, 8 h per day) for 7 days (n=16) while control rats (n=18) were maintained in normoxia. Baroreflex regulation of RSNA and HR were estimated in Inactin anesthetized and artificially ventilated rats during infusions of phenylephrine and nitroprusside to manipulate AP. After exposure to CIH, resting mean AP was higher in CIH than that in control group (115±7 vs. 105±7, P<0.001). Resting HR did not differ between the two groups. Exposure to CIH shifted the AP-RSNA relationship rightward (approximately 10 mm Hg, P<0.01). CIH did not alter maximum gain of the baroreflex control of RSNA (-2.6±0.6 vs. -2.5±0.6 arbitrary units (a.u.)/mm Hg) and HR (-1.8±0.6 vs. -1.8±0.7 bpm/mm Hg, CIH vs. control). In addition, cardiac spontaneous baroreflex sensitivity in conscious rats (n=8) also did not change during exposure to CIH. These results indicate that resetting of the sympathetic baroreflex control, rather than an impairment of its sensitivity, is associated with an onset of hypertension induced by CIH.

Figure 1

Percentage of oxygen in the chronic intermittent hypoxia (CIH) chambers. Oxygen was maintained at 9 % for 3 min in each hypoxia cycle. Exposure to CIH occurred for 8 hrs during the light period (8:00 to 16:00) for 7 days.

Figure 2

Typical recordings of AP, renal sympathetic nerve activity [SNA; in arbitrary units (a.u.)], and HR obtained in anesthetized rat. The rate of infusion was adjusted to produce continuous changes in AP at 1 mmHg/s. Data in this figure were resampled at 10 Hz. White lines in the SNA panels were resampled at 1 Hz. Raw data was sampled at 1000 Hz.

Figure 3

Mean arterial pressure (MAP), heart rate (HR), spontaneous baroreflex sensitivity (SBRS) and respiratory frequency (Resp Freq) in the light period (A, C, E and G) and the dark period (B, D, F and H) in conscious rats. Between vertical dashed lines indicates during exposure to CIH. The open and closed circles represent data points obtained from control and CIH groups, respectively. MAP increased after exposure to CIH in the both light and dark periods. HR, SBRS and respiratory frequency did not differ between before and after exposure to CIH. *P<0.01 compared with before CIH within same group.

Figure 4

Baroreflex control of SNA (A: baseline = 100 au, B: maximum = 100 au) and HR (C) averaged for the control (n = 18) and CIH (n = 16) rats in anesthetized rats. After exposure to CIH, the AP-SNA relationship shifted rightward (Table 1). Baroreflex parameters in the AP-HR relationship did not differ statistically between control and CIH rats.

Figure 5

Relationship between MAP and midpoint pressure (A) or maximum gain (B) in AP-SNA relationship. The midpoint pressure correlated with resting MAP. The maximum gain did not correlate with MAP.