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Comparative Study
. 2014 Jan 23;9(1):e86868.
doi: 10.1371/journal.pone.0086868. eCollection 2014.

Cardiovascular responses induced by obstructive apnea are enhanced in hypertensive rats due to enhanced chemoreceptor responsivity

Juliana M M Angheben  1 , Guus H M Schoorlemmer  1 , Marcio V Rossi  1 , Thiago A Silva  1 , Sergio L Cravo  1
Affiliations
Comparative Study

Cardiovascular responses induced by obstructive apnea are enhanced in hypertensive rats due to enhanced chemoreceptor responsivity

Juliana M M Angheben et al. PLoS One. .

Abstract

Spontaneously hypertensive rats (SHR), like patients with sleep apnea, have hypertension, increased sympathetic activity, and increased chemoreceptor drive. We investigated the role of carotid chemoreceptors in cardiovascular responses induced by obstructive apnea in awake SHR. A tracheal balloon and vascular cannulas were implanted, and a week later, apneas of 15 s each were induced. The effects of apnea were more pronounced in SHR than in control rats (Wistar Kyoto; WKY). Blood pressure increased by 57±3 mmHg during apnea in SHR and by 28±3 mmHg in WKY (p<0.05, n = 14/13). The respiratory effort increased by 53±6 mmHg in SHR and by 34±5 mmHg in WKY. The heart rate fell by 209±19 bpm in SHR and by 155±16 bpm in WKY. The carotid chemoreceptors were then inactivated by the ligation of the carotid body artery, and apneas were induced two days later. The inactivation of chemoreceptors reduced the responses to apnea and abolished the difference between SHR and controls. The apnea-induced hypertension was 11±4 mmHg in SHR and 8±4 mmHg in WKY. The respiratory effort was 15±2 mmHg in SHR and 15±2 mmHg in WKY. The heart rate fell 63±18 bpm in SHR and 52±14 bpm in WKY. Similarly, when the chemoreceptors were unloaded by the administration of 100% oxygen, the responses to apnea were reduced. In conclusion, arterial chemoreceptors contribute to the responses induced by apnea in both strains, but they are more important in SHR and account for the exaggerated responses of this strain to apnea.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Cardiovascular and respiratory responses induced by obstructive apnea in rats.
Representative recordings of arterial pressure (AP), electrocardiogram (ECG), mean arterial pressure (MAP), heart rate (HR) and thoracic pressure (TP) over 15 s of apnea in (A) a normotensive Wistar Kyoto rat (WKY) and (B) a spontaneously hypertensive rat (SHR).
Figure 2
Figure 2. Cardiovascular and respiratory responses induced by obstructive apnea in rats.
A. Arterial pressure, heart rate, and breathing effort (measured as thoracic pressure swing) in SHR (n = 14) and WKY (n = 13) over 15 s of apnea. Error bars indicate SEM. MAP  =  mean arterial pressure, HR  =  heart rate, TP  =  thoracic pressure. B. Average change during the apnea period. * indicates a difference between strains (Bonferroni test, p<0.05).
Figure 3
Figure 3. Changes in blood gases during apnea.
Arterial blood gases before and after 10 to 15 seconds of apnea in WKY (n = 5) and SHR (n = 5). Error bars indicate SEM. * indicates a difference from the pre-apnea level. † indicates a difference between strains (Bonferroni, p<0.05).
Figure 4
Figure 4. Effect of bilateral ligation of the carotid body arteries on responses induced by cyanide.
A. Changes in mean arterial pressure, heart rate and thoracic pressure induced by the i.v. injection of 40 µg potassium cyanide (KCN) in WKY (n = 13) and SHR (n = 14) before and two days after section of the carotid body arteries. Error bars indicate SEM. MAP  =  mean arterial pressure, HR  =  heart rate, TP =  thoracic pressure. B. Peak responses during the KCN test. * indicates a difference from the pre-ligation value (Bonferroni, p<0.05).
Figure 5
Figure 5. Role of carotid chemoreceptors in responses induced by obstructive apnea.
A. Apnea-induced responses in WKY (n = 13) and SHR (n = 14) rats, before and two days after section of the carotid body arteries. Error bars indicate SEM. MAP  =  mean arterial pressure, HR  =  heart rate, TP  =  thoracic pressure. B. Average responses to apnea. * indicates difference from before inactivation; † indicates difference between strains (Bonferroni, p<0.05).
Figure 6
Figure 6. Hyperoxia attenuates apnea-induced responses.
A. Changes in mean arterial pressure, heart rate and thoracic pressure in WKY and SHR rats during apnea in normoxia (21% O2) and hyperoxia (100% O2). Error bars indicate SEM. MAP  =  mean arterial pressure, HR  =  heart rate, TP  =  thoracic pressure. B. Average responses to apnea in WKY (n = 13) and SHR (n = 14) during apnea in normoxia and hyperoxia. Error bars indicate SEM. * indicates a difference from 21%; † indicates a difference between strains (Bonferroni, p<0.05).
Figure 7
Figure 7. After inactivation of peripheral chemoreceptors, there is no longer a difference between the responses to apnea in 21% and 100% oxygen.
A. Effect of hyperoxia on apnea-induced changes in mean arterial pressure, heart rate and thoracic pressure in WKY and SHR rats with surgically inactivated chemoreceptors. Error bars indicate SEM. MAP  =  mean arterial pressure, HR  =  heart rate, TP  =  thoracic pressure. B. Average responses to apnea in WKY (n = 13) and SHR (n = 14) during apnea in normoxia and hyperoxia, both after inactivation of chemoreceptors. † indicates a difference between strains (Bonferroni, p<0.05).
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