The Beneficial Impact of Fasudil and Sildenafil on Monocrotaline-Induced Pulmonary Hypertension in Rats: A Hemodynamic and Biochemical Study

Abstract

Pulmonary arterial hypertension (PAH) still cannot be cured effectively, hence the search for novel treatments continues. The effects of sildenafil (25 mg/kg body weight) and fasudil (30 mg/kg body weight) given alone or in combination, on normalization of right ventricular pressure (RVP), right ventricle mass, as well as the levels of several biomarkers (HDL-C, BNP, VEGF-A), were assessed in a rat model of monocrotaline (MCT)-induced PAH. MCT (60 mg/kg body weight) induced clear PAH in male Wistar rats. After 21 days, a significant decrease in RVP accompanied by a reduction of right ventricular hypertrophy - a significant decrease in the right ventricle/left ventricle plus septum ratio - as a result of sildenafil or fasudil administration was assessed. The administration of fasudil and sildenafil alone or in combination caused a significant decrease in plasma BNP level as compared to MCT-treated rats. Fasudil alone or with sildenafil, but not sildenafil alone, significantly increased HDL-C level as compared to MCT-treated rats. Fasudil and sildenafil given alone or in combination caused a significant increase in plasma VEGF-A level as compared to rats exposed to MCT.

Rosuvastatin, Sildenafil and Their Combination in Monocrotaline-Induced Pulmonary Hypertension in Rat

“…Although this is confirmed for BNP, it is only discussed for VEGF-A. The role of such factors in pulmonary hypertension, together with several mechanistic implications, has been previously discussed (16).…”

“…Lidocaine was used for local infiltration of the surgical sites. The registration of hemodynamic parameters in rats was performed by using a Hugo Sachs Electronik Haemodyn (Harvard Apparatus GmbH, Germany), as described previously (16).…”

Concurrent Rho-Kinase and Tyrosine Kinase Platelet-Derived Growth Factor Inhibition in Experimental Pulmonary Hypertension

“…Only the combination therapy with beraprost showed significantly more improvement in PAH or right ventricular hypertrophy. Compared to endothelin receptor blockade by bosentan and PDE5 inhibition by sildenafil, fasudil was equally or more effective, but combination therapy had no complementary effects compared to fasudil alone [16,25,26]. …”

“…Lidocaine was used for local infiltration of the surgical sites. The registration of hemodynamic parameters in rats was performed by using a Hugo Sachs Elektronik Haemodyn (Harvard Apparatus GmbH, March, Germany), as described previously [16]. …”

HMG-COA reductase inhibitors: An opportunity for the improvement of imatinib safety. An experimental study in rat pulmonary hypertension

“…Lidocaine was used for local infiltration of the surgical sites. The registration of hemodynamic parameters in rats was performed by using a Hugo Sachs Electronik Haemodyn (Harvard Apparatus GmbH, March, Germany), as described previously [21]. In brief, for the right ventricular pressure (RVP) measurement, the catheter was inserted through the right jugular vein and advanced into the right ventricle.…”