Riociguat

Animal experiment:

Mice[1] For chronic intervention studies four groups of mice are used: control mice exposed for 35 days to normoxic gas (n=10); mice exposed for 21 days to hypoxic gas (n=10); mice exposed for 35 days to hypoxic gas and who receives the vehicle (2% methylcellulose solution) from day 21 to day 35 (n=10); and mice exposed for 35 days to hypoxic gas and who receives BAY 63-2521 (10 mg/kg) once a day by oral application (n=10) from day 21 to day 35. For continuous measurement of Prvs and cardiac frequency by radiotelemetry, a separate group of mice is exposed for 35 days to hypoxic gas and receives BAY 63-2521 (10 mg/kg) once a day by oral application from day 21 to day 35. In order to investigate vascular reactivity in isolated mouse lungs, an additional two groups of animals are investigated: control mice (n=12) and animals exposed for 21 days to hypoxic conditions (n=12). Rats[1] Rats are randomised for chronic BAY 63-2521 treatment, 21 days after MCT injection. The experimental groups includes rats that receives BAY 63-2521 (10 mg/kg) or vehicle (2% methylcellulose solution) by oral application, once per day. Rats are examined daily and subjected to haemodynamic measurements and histological assessment at day 35.

References:

[1]. Schermuly RT, et al. Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension. Eur Respir J. 2008 Oct;32(4):881-91.
[2]. Schermuly RT, et al. Riociguat for the treatment of pulmonary hypertension. Expert Opin Investig Drugs. 2011 Apr;20(4):567-76.
[3]. Donda K, et al. Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth. PLoS One. 2018 Jul 10;13(7):e0199927.