• Asymmetric dimethylarginine;
  • Dog;
  • Endothelial dysfunction


Cardiovascular disease is associated with endothelial dysfunction in humans and studies of plasma biomarkers suggest that dogs with myxomatous mitral valve disease (MMVD) might also have endothelial dysfunction.


That progression of mitral regurgitation (MR) is associated with development of endothelial dysfunction.


Forty-three Cavalier King Charles Spaniels (CKCS) with MR of varying severity.


Privately owned CKCS were prospectively recruited and divided in 4 groups: (1) 12 CKCS with minimal MR; (2) 9 CKCS with mild MR; (3) 11 CKCS with moderate-severe MR; and (4) 11 CKCS with moderate-severe MR and clinical signs compatible with heart failure. Dogs underwent blood sampling, echocardiography, blood pressure (BP) recordings, and flow-mediated vasodilation (FMD) measurements. The effect of progressive MR on FMD was determined by multivariate analyses.


Flow-mediated vasodilation decreased with progression of MR. Group 4 (4.79 ± 3.22%) had significantly lower FMD than groups 1 (10.40 ± 4.58%) and 2 (10.14 ± 3.67%) (< .005) and group 3 (6.79 ± 3.98%) had a significantly lower FMD than group 1 (= .03). Increasing left ventricular end-diastolic diameter (= .0004, R2 = 0.27) and the combination of age (= .01) and body weight (= .002) (R2 = 0.31) were significantly associated with reduced FMD. FMD did not correlate with sex, BP, or plasma markers.

Conclusions and Clinical Importance

Reduced FMD indicates that increased disease severity in CKCS with MMVD is associated with development of endothelial dysfunction which might be a future therapeutic and/or diagnostic target.