Muscarinic cholinergic modulation of cardiovascular variables in spinal cord injured rats

Théo Mille (1), Aurélie Bonilla (1), Etienne Guillaud(1), Sandrine Bertrand (1), Clément Menuet (2),
Jean-René Cazalets (3).

Author information:
(1)Université de Bordeaux, CNRS UMR 5287, INCIA, Zone nord, Bat 2, 2e étage, 146
rue Léo Saignat, 33076 Bordeaux cedex, France.
(2)Institut de Neurobiologie de la Méditerranée, INMED UMR 1249, INSERM,
Aix-Marseille Université, Marseille, France.
(3)Université de Bordeaux, CNRS UMR 5287, INCIA, Zone nord, Bat 2, 2e étage, 146
rue Léo Saignat, 33076 Bordeaux cedex, France. Electronic address:
.

Spinal cord injury (SCI) leads not only to major impairments in sensorimotor
control but also to dramatic dysregulation of autonomic functions including
major cardiovascular disturbances. Consequently, individuals with SCI endure
daily episodic hypo/hypertension and are at increased risk for cardiovascular
disease. Several studies have suggested that an intrinsic spinal coupling
mechanism between motor and sympathetic neuronal networks exist and that
propriospinal cholinergic neurons may be responsible for a synchronized
activation of both somatic and sympathetic outputs. We therefore investigated in
the present study, the effect of cholinergic muscarinic agonists on
cardiovascular parameters in freely moving adult rats after SCI. Female
Sprague-Dawley rats were implanted with radiotelemetry sensors for long-term in
vivo monitoring of blood pressure (BP). From BP signal, we calculated heart rate
(HR) and respiratory frequency. We first characterized the physiological changes
occurring after a SCI performed at the T3-T4 level in our experimental model
system. We then investigated the effects on BP, HR and respiration, of the
muscarinic agonist oxotremorine using one variant that crossed the blood brain
barrier (Oxo-S) and one that does not (Oxo-M) in both Pre- and Post-SCI animals.
After SCI, both HR and respiratory frequency increased. BP values exhibited an
immediate profound drop before progressively increasing over the three-week
post-lesion period but remained below control values. A spectral analysis of BP
signal revealed the disappearance of the low frequency component of BP
(0.3-0.6 Hz) referred to as Mayer waves after SCI. In Post-SCI animals, central
effects mediated by Oxo-S led to an increase in HR and MAP, a slowdown in
respiratory frequency and to an increased power in the 0.3-0.6 Hz frequency
band. This study unravels some of the mechanisms by which muscarinic activation
of spinal neurons could contribute to partial restoration of BP after SCI.

Copyright © 2023 Elsevier Inc. All rights reserved.

Conflict of interest statement: Declaration of Competing Interest The authors
declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this
paper.

Know more about