The Effects of Cyclic Guanylate Cyclase Stimulation on Right Ventricular Hypertrophy and Failure Alone and in Combination With Phosphodiesterase-5 Inhibition

Abstract

Stimulation of soluble guanylate cyclase by BAY 41-2272 alone or in combination with sildenafil failed to prevent the development of RV hypertrophy and failure in rats subjected to pulmonary trunk banding. An increased mortality was observed in animals treated by BAY 41-2272 alone and in combination with sildenafil.

Effects of Bisoprolol and Losartan Treatment in the Hypertrophic and Failing Right Heart

“…19 We observed TR in most of the PTB rats banded with a 0.6-mm clip and in all of the PTB rats banded with a 0.5-mm clip. Tricuspid regurgitation is a significant pathologic factor in PAH and an independent risk factor of transplantation or death in PAH patients.…”

“…19 Rats were sedated, intubated, and mechanically ventilated with sevoflurane (Abbot Scandinavia, Solona, Sweden; induction: 7.0% in 2:1 O 2 /N 2 O mix; maintenance: 3.5% in 2:1 O 2 /N 2 O mix) at 75 breaths/min and a tidal volume of 10 mL/kg. A lateral thoracotomy was performed and the pulmonary trunk and the aorta carefully separated, enabling the appliance of a titanium clip with an inner diameter of 0.5 mm or 0.6 mm around the pulmonary trunk.…”

New insights into the role of soluble guanylate cyclase in blood pressure regulation

“…Sodium nitrite therapy also improves the outcome in monocrotaline-induced pulmonary hypertension in the rat via sGC activation after conversion of nitrite to vasoactive NO [40]. On the other hand, stimulation of sGC by the riociguat-related stimulator BAY 41-2272, with or without inhibition of cGMP phosphodiesterase by sildenafil administration, fails to prevent right ventricle hypertrophy after pulmonary trunk banding in rats [41]. A likely explanation for the discrepancy between these studies is that the surgical procedure performed in the latter study directly induces right ventricular hypertrophy, while the other studies rely on models of primary pulmonary vascular dysfunction.…”

Comment on “Effect of Riociguat and Sildenafil on Right Heart Remodeling and Function in Pressure Overload Induced Model of Pulmonary Arterial Banding”

“…It is an important topic and by using magnetic resonance imaging (MRI) to characterize right ventricular (RV) performance it adds to previous studies on the same subject [2–6]. The authors conclude that both sildenafil and riociguat prevent RV failure in mice subjected to pulmonary artery banding (PAB) based on improvement in stroke volume (SV) and ejection fraction (EF).…”

“…Another comment is that previous studies with a similar design in a rat PAB model [6] found that mortality was increased with the soluble guanylate cyclase (sGC) stimulator BAY 41-2272 (a compound similar to riociguat). It should be reported in the paper by Rai and colleagues whether there was any mortality in the treatment arms in this study, as this could potentially introduce a selection bias.…”