AUTHOR=Järve Anne , Todiras Mihail , Kny Melanie , Fischer Falk I. , Kraemer Jan F. , Wessel Niels , Plehm Ralph , Fielitz Jens , Alenina Natalia , Bader Michael TITLE=Angiotensin-(1-7) Receptor Mas in Hemodynamic and Thermoregulatory Dysfunction After High-Level Spinal Cord Injury in Mice: A Pilot Study JOURNAL=Frontiers in Physiology VOLUME=9 YEAR=2019 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.01930 DOI=10.3389/fphys.2018.01930 ISSN=1664-042X ABSTRACT=

Spinal cord injury (SCI) above mid-thoracic levels leads to autonomic dysfunction affecting both the cardiovascular system and thermoregulation. The renin-angiotensin system (RAS) which is a potent regulator of blood pressure, including its novel beneficial arm with the receptor Mas could be an interesting target in post-SCI hemodynamics. To test the hypothesis that hemodynamics, activity and diurnal patterns of those are more affected in the Mas deficient mice post-SCI we used a mouse model of SCI with complete transection of spinal cord at thoracic level 4 (T4-Tx) and performed telemetric monitoring of blood pressure (BP) and heart rate (HR). Our data revealed that hypothermia deteriorated physiological BP and HR control. Preserving normothermia by keeping mice at 30°C prevented severe hypotension and bradycardia post-SCI. Moreover, it facilitated rapid return of diurnal regulation of BP, HR and activity in wild type (WT) mice. In contrast, although Mas deficient mice had comparable reacquisition of diurnal HR rhythm, they showed delayed recovery of diurnal rhythmicity in BP and significantly lower nocturnal activity. Exposing mice with T4-Tx (kept in temperature-controlled cages) to 23°C room temperature for one hour at different time-points post-SCI, demonstrated their inability to maintain core body temperature, Mas deficient mice being significantly more impaired than WT littermates. We conclude that Mas deficient mice were more resistant to acute hypotension, delayed nocturnal recovery, lower activity and more severely impaired thermoregulation. The ambient temperature had significant effect on hemodynamics and, thus it should be taken into account when assessing cardiovascular parameters post-SCI in mice.