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1. PreBötzinger complex neurons drive respiratory modulation of blood pressure and heart rate

Author

Clément Menuet, Angela A Connelly, Jaspreet K Bassi, Mariana R Melo, Sheng Le, Jessica Kamar, Natasha N Kumar, Stuart J McDougall, Simon McMullan, and Andrew M Allen

Subjects
prebötzinger complex, master oscillator, cardiorespiratory control, respiratory sinus arrhythmia, respiratory-sympathetic modulation, optogenetic inhibition, Medicine, Science, Biology (General), QH301-705.5
Abstract

Heart rate and blood pressure oscillate in phase with respiratory activity. A component of these oscillations is generated centrally, with respiratory neurons entraining the activity of pre-sympathetic and parasympathetic cardiovascular neurons. Using a combination of optogenetic inhibition and excitation in vivo and in situ in rats, as well as neuronal tracing, we demonstrate that preBötzinger Complex (preBötC) neurons, which form the kernel for inspiratory rhythm generation, directly modulate cardiovascular activity. Specifically, inhibitory preBötC neurons modulate cardiac parasympathetic neuron activity whilst excitatory preBötC neurons modulate sympathetic vasomotor neuron activity, generating heart rate and blood pressure oscillations in phase with respiration. Our data reveal yet more functions entrained to the activity of the preBötC, with a role in generating cardiorespiratory oscillations. The findings have implications for cardiovascular pathologies, such as hypertension and heart failure, where respiratory entrainment of heart rate is diminished and respiratory entrainment of blood pressure exaggerated.

Published
2020
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3. Excessive Respiratory Modulation of Blood Pressure Triggers Hypertension

Author

Simon McMullan, Angela A. Connelly, Jessica Kamar, Angelina Y. Fong, Annabel E. Simms, Clément Menuet, Ann K. Goodchild, Jaspreet K. Bassi, Bowen Dempsey, Andrew M. Allen, Keryn Walters, Sheng Le, Nikola Jancovski, and Andrew Hammond

Subjects
Aging, medicine.medical_specialty, Sympathetic nervous system, Sympathetic Nervous System, Physiology, Blood Pressure, 030204 cardiovascular system & hematology, Lesion, 03 medical and health sciences, 0302 clinical medicine, Rats, Inbred SHR, Internal medicine, Renin–angiotensin system, medicine, Animals, Molecular Biology, Neurons, business.industry, Respiration, Cell Biology, Rostral ventrolateral medulla, medicine.disease, Endocrinology, Blood pressure, medicine.anatomical_structure, Pathophysiology of hypertension, Hypertension, Synapses, Medulla oblongata, Carotid body, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

The etiology of hypertension, the world's biggest killer, remains poorly understood, with treatments targeting the established symptom, not the cause. The development of hypertension involves increased sympathetic nerve activity that, in experimental hypertension, may be driven by excessive respiratory modulation. Using selective viral and cell lesion techniques, we identify adrenergic C1 neurons in the medulla oblongata as critical for respiratory-sympathetic entrainment and the development of experimental hypertension. We also show that a cohort of young, normotensive humans, selected for an exaggerated blood pressure response to exercise and thus increased hypertension risk, has enhanced respiratory-related blood pressure fluctuations. These studies pinpoint a specific neuronal target for ameliorating excessive sympathetic activity during the developmental phase of hypertension and identify a group of pre-hypertensive subjects that would benefit from targeting these cells.

Published
2017
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