Respiratory training of cardiovascular activity: a central control generated at the core of the neuronal respiratory network

Introduction: Heart rate and blood pressure fluctuate in phase with respiratory activity. This coupling between respiratory and cardiovascular activities optimises gas exchange and heart work. It is mostly controlled centrally, where brainstem neurons generating the respiratory command modulate the activity of pre‐sympathetic and pre‐parasympathetic cardiovascular neurons; however, little is known about the precise circuitry involved.

Methods: We used a combination of optogenetic techniques in animal models.

Results: Using inhibition and excitation in rats in vivo and in situ, as well as neuronal tracing, we demonstrate that a group of respiratory neurons that is the kernel for respiratory rhythm generation (the preBötzinger Complex, preBötC) directly modulates both sympathetic and parasympathetic activities. Specifically, a subgroup of preBötC neurons provides a strong respiratory phasic and tonic inhibitory drive to cardiac preganglionic parasympathetic neurons, generating respiratory sinus arrhythmia (heart rate oscillations in phase with respiratory activity). Also, a subgroup of preBötC neurons provides an excitatory drive to sympathetic vasomotor neurons, generating Traube‐Hering waves (blood pressure oscillations in phase with respiratory activity). We confirm the primary role of the preBötC for respiratory rhythm generation, and we further show that it determines the duration of the different phases of the respiratory cycle.

Conclusion: Overall, our data reveal the neuronal circuit, generating the respiratory exercise of heart rate and blood pressure, showing that the preBötC is more than the kernel for respiratory rhythm generation, it serves as a cardiorespiratory oscillator. This is of primary physiological and pathological relevance, respiratory sinus arrhythmia being abolished and Traube‐Hering waves exacerbated in major cardiovascular diseases such as hypertension and heart failure.