Angiotensin‐II receptor type Ia does not contribute to cardiac atrophy following high‐thoracic spinal cord injury in mice


  • A. Järve
  • F. Qadri
  • M. Todiras
  • S. Schmolke
  • M. Bader


  • Experimental Physiology


  • Exp Physiol 105 (8): 1316-1325


  • NEW FINDINGS: What is the central question of this study? Spinal cord injury leads to cardiac atrophy and the role of the renin-angiotensin system with angiotensin II acting via its receptor AT1a in this effect has not been previously explored. What is the main finding and its importance? In mice undergone thoracic level 4 transection, we confirm cardiac atrophy. Knockout of AT1a does not protect mice from cardiac atrophy. We observed no histopathological signs but reduced load-dependent left ventricular function (lower stroke volume and cardiac output) with preserved ejection fraction. Further investigations are warranted to assess cardiac function under stress conditions. ABSTRACT: Spinal cord injury (SCI) leads to cardiac atrophy often accompanied by functional deficits. The renin-angiotensin system (RAS) with angiotensin II (AngII) signalling via its receptor AT1a might contribute to cardiac atrophy post-SCI. We performed spinal cord transection at thoracic level T4 (T4-Tx) or sham-operation in female wild type mice (WT, n = 27) and mice deficient of AT1a (Agtr1a(-/-), n = 27). Echocardiography (0, 7, 21 and 28 days post-SCI) as well as histology and gene expression analyses at 1 and 2 months post-SCI were performed. We found cardiac atrophy post-SCI: reduced heart weight, estimated left ventricular mass in Agtr1a(-/-), and cardiomyocyte diameter in WT mice. Although, the latter as well as stroke volume (SV) and cardiac output (CO) were reduced in Agtr1a(-/-) mice already at baseline, cardiomyocyte diameter was even smaller in injured Agtr1a(-/-) mice compared to injured WT mice. SV and CO were reduced in WT mice post-SCI. Ejection fraction and fractional shortening was preserved post-SCI in both genotypes. There were no histological signs of fibrosis and pathology in the cardiac sections of both genotypes post-SCI. Gene expression of Agtr1a showed a trend for upregulation at 2 months post-SCI, angiotensinogen was upregulated at 2 month post-SCI in both genotypes. AngII receptor type 2 (Agtr2) was up-and down-regulated at 1 and 2 months post-SCI in WT mice, respectively, and Ang-(1-7) receptor (Mas) at 1 and 2 months post-SCI. Atrogin-1/MAFbx and MuRF1, the atrophy markers were not significantly upregulated post-SCI. Our data shows that lack of AT1a does not protect from cardiac atrophy post-SCI.