Deactivation of carotid body chemoreceptors by hyperoxia decreases blood pressure in hypertensive patients

Periodic breathing has been found in patients with heart failure and sleep apneas, and in healthy subjects in hypoxia, during sleep and wakefulness, at rest and, recently, at exercise. To unravel the cardiorespiratory parameters liable to modulate the amplitude and period of ventilatory oscillations, 26 healthy subjects were tested under physiological (exercise) and environmental (hypoxia, hyperoxia, hyperoxic hypercapnia) stresses, and under acetazolamide (ACZ) treatment. A fast Fourier transform spectral analysis of breath-by-breath ventilation evidenced an increase in peak power under hypercapnia (vs. normoxia and hyperoxia, P < 0.001) and a decrease under ACZ (vs. placebo, P < 0.001), whereas it was not modified in hyperoxia. period was shortened by exercise in all conditions (vs. rest, P < 0.01) and by hypercapnia (vs. normoxia, P < 0.05) but remained unchanged under ACZ (vs. placebo). peak power was positively related to cardiac output () and in hyperoxia (P < 0.01), in hypercapnia (P < 0.001) and under ACZ (P < 0.001). period was negatively related to and in hyperoxia (P < 0.01 and P < 0.001, respectively), in hypercapnia (P < 0.05 and P < 0.01, respectively) and under ACZ (P < 0.05 and P < 0.01, respectively). Total respiratory cycle time was the main factor responsible for changes in period. In conclusion, exercise, hypoxia, and hypercapnia increase ventilatory oscillations by increasing and , whereas ACZ decreases ventilatory instability in part by a contrasting action on O2 and CO2 sensing. An intrinsic oscillator might modulate ventilation through a complex system where peripheral chemoreflex would play a key role.

show abstract

“…Hyperoxia, which silences peripheral chemoreceptors (Sinski et al. ), did not modify

\dot{normalV} E

peak power and therefore

\dot{normalV} E

oscillations in healthy subjects, in accordance with some but not all studies in patients with mixed sleep apnea (Brack et al. ).…”

Section: Discussionsupporting

confidence: 81%

Ventilatory oscillations at exercise: effects of hyperoxia, hypercapnia, and acetazolamide

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Despite the inevitable surgical damage to the mechanoreceptors and associated afferents, baroreceptor function improved. Also, in humans, brief exposure to oxygen lowers SBP, presumably due to sympathetic effects subsequent to inactivation of the chemoreflex 16 .…”

Section: Discussionmentioning

confidence: 99%

“…In human essential hypertensive subjects: a) the CBs are hypersensitive to chemical stimuli compared to those of their normotensive counterparts 13 , b) surgical CB removal reduces blood pressure (BP) in subjects with comorbid asthma 3, 14 and c) hyperoxia reduces BP in otherwise untreated subjects 15, 16 . A pivotal single-arm, unblinded trial testing the effects of surgical and interventional CB resection on human resistant HTN is ongoing in Europe (clinicaltrials.gov identifier: NCT01745172/NCT02099851).…”

Section: Introductionmentioning

confidence: 99%

Effects of carotid body tumor resection on the blood pressure of essential hypertensive patients

Fudim

Groom

Laffer

et al. 2015

Journal of the American Society of Hypertension

View full text Add to dashboard Cite

Removal of the carotid body (CB) improves animal models of hypertension (HTN) and heart failure, presumably via withdrawal of chemoreflex-induced sympathetic activation. The effect of CB tumor (CBT) resection on blood pressure (BP) in subjects with HTN is unknown. We conducted a retrospective analysis of 20 subjects with HTN (BP≥140/90 mmHg or use of antihypertensives) out of 134 who underwent CBT resection. Short-term (from 3 months before to the first reading after 30 days from surgery) and long-term (slope of the regressions on time over the entire follow up) changes in BP and heart rate (HR) were ascertained and adjusted for covariates (interval between readings, total follow up, number of readings and changes in therapy). Age and duration of HTN were 56±4 and 9±5 years. Adjusted short-term decreases in systolic (SBP: −9.9±3.1, p<0.001) and pulse pressures (PP: −7.9±2.7, p<0.002) were significant and correlated with their respective long-term changes (SBP: r=0.47, p=0.047; PP: r=0.54, p=0.019). Also, there was a strong relationship between adjusted short-term changes in SBP and PP (r=0.64, p<0.004). Out of 12 subjects with concordant decreases in short-and long-term BP changes, 6 (50% of responders or 33% of the total) had short-term falls of SBP ≥10 mmHg and of PP ≥ 5mmHg. To our knowledge this study is the first to show that unilateral CBT resection is associated with sustained reduction of BP in subjects with HTN. Hence, we suggest that targeted removal of the CB chemoreflex conceivably has a role in the therapy of human HTN.

show abstract

“…177 It has also been shown that hyperoxia decreases BP acutely in patients with hypertension, but not in normotensive controls. 178 These data point to a potential pathogenetic role of tonic chemoreceptor drive in the development of sympathetic overactivity in hypertension. 177 Surgical removal of the CB has been performed in humans for reasons other than hypertension (eg, bronchial asthma and chronic obstructive pulmonary disease [COPD]).…”

Section: Carotid Body Ablationmentioning

confidence: 99%

New Approaches in the Treatment of Hypertension

Oparil

Schmieder

2015

Circulation Research

237

137

View full text Add to dashboard Cite

Hypertension is the most common modifiable risk factor for cardiovascular disease and death, and lowering blood pressure with antihypertensive drugs reduces target organ damage and prevents cardiovascular disease outcomes. Despite a plethora of available treatment options, a substantial portion of the hypertensive population has uncontrolled blood pressure. The unmet need of controlling blood pressure in this population may be addressed, in part, by developing new drugs and devices/procedures to treat hypertension and its comorbidities. In this Compendium Review, we discuss new drugs and interventional treatments that are undergoing preclinical or clinical testing for hypertension treatment. New drug classes, eg, inhibitors of vasopeptidases, aldosterone synthase and soluble epoxide hydrolase, agonists of natriuretic peptide A and vasoactive intestinal peptide receptor 2, and a novel mineralocorticoid receptor antagonist are in phase II/III of development, while inhibitors of aminopeptidase A, dopamine β-hydroxylase, and the intestinal Na + /H + exchanger 3, agonists of components of the angiotensin-converting enzyme 2/angiotensin(1–7)/Mas receptor axis and vaccines directed toward angiotensin II and its type 1 receptor are in phase I or preclinical development. The two main interventional approaches, transcatheter renal denervation and baroreflex activation therapy, are used in clinical practice for severe treatment resistant hypertension in some countries. Renal denervation is also being evaluated for treatment of various comorbidities, eg, chronic heart failure, cardiac arrhythmias and chronic renal failure. Novel interventional approaches in early development include carotid body ablation and arteriovenous fistula placement. Importantly, none of these novel drug or device treatments has been shown to prevent cardiovascular disease outcomes or death in hypertensive patients.

show abstract

Deactivation of carotid body chemoreceptors by hyperoxia decreases blood pressure in hypertensive patients

Cited by 48 publications

References 31 publications

Ventilatory oscillations at exercise: effects of hyperoxia, hypercapnia, and acetazolamide

Ventilatory oscillations at exercise: effects of hyperoxia, hypercapnia, and acetazolamide

Effects of carotid body tumor resection on the blood pressure of essential hypertensive patients

New Approaches in the Treatment of Hypertension

Contact Info

Product

Resources

About