A recent study evaluated the effect of chronic losartan treatment for 9 months on muscle wasting in two mouse models - dysferlin-null mice fed a control diet, and dysferlin-null mice fed a high-fat Western diet (HFD).

Losartan was shown to increase quadriceps muscle fibrosis (142%) in a mild, dysferlin-null mouse model of Limb-Girdle muscular dystrophy (MD) type 2B (LGMD2B). In a severe, atherogenic diet-fed model of LGMD2B, losartan further aggravated dysferlin-null mouse muscle wasting in quadriceps and triceps brachii by 40% and 51%, respectively. Losartan was not associated with lower TGF-β signalling. Losartan was also found to increase plasma triglycerides and cholesterol concentrations in dysferlin-null mice. In the absence of dysferlin expression, other protective properties of losartan, including increased nitric oxide release and BP lowering, were found to be reduced.

LGMD2B patients may exhibit resistance to the primary BP-lowering effects of losartan along with accelerated muscle wasting and dyslipidemia. Researchers thus cautioned on the use of ARBs in this population due to the possibility of a flawed ATR1 pathway.

Source: White Z, Milad N, Tehrani AY, et al. Angiotensin II receptor blocker losartan exacerbates muscle damage and exhibits weak blood pressure-lowering activity in a dysferlin-null model of Limb-Girdle muscular dystrophy type 2B. PLoS One. 2019 Aug 12;14(8):e0220903.