In a canine model of heart failure, BAY 41-2272 significantly reduced mean arterial pressure (113 to 94 mm Hg; P<0.05) and increased cardiac output (2.1 to 2.3 L/min; P<0.05).
Does intravenous BAY 41-2272 improve cardiorenal and humoral function in a canine model of congestive heart failure?
The direct sGC stimulator BAY 41-2272 potently unloads the heart, increases cardiac output, and preserves glomerular filtration rate without activating the renin-angiotensin-aldosterone system in a canine model of congestive heart failure.
BACKGROUND: BAY 41-2272 is a recently introduced novel orally available agent that directly stimulates soluble guanylate cyclase (sGC) and sensitizes it to its physiological stimulator, nitric oxide. To date, its therapeutic actions in congestive heart failure (CHF) remain undefined. We characterized the cardiorenal actions of intravenous BAY 41-2272 in a canine model of CHF and compared it to nitroglycerin (NTG). METHODS AND RESULTS: CHF was induced by rapid ventricular pacing for 10 days. Cardiorenal and humoral function were assessed at baseline and with administration of 2 doses of BAY 41-2272 (2 and 10 micro g x kg(-1) x min(-1); n=8) or NTG (1 and 5 micro g x kg(-1) x min(-1); n=6). Administration of 10 micro g x kg(-1) x min(-1) BAY 41-2272 reduced mean arterial pressure (113+/-8 to 94+/-6 mm Hg; P<0.05), pulmonary artery pressure (29+/-2 to 25+/-2 mm Hg; P<0.05), and pulmonary capillary wedge pressure (25+/-2 to 20+/-2 mm Hg; P<0.05). Cardiac output (2.1+/-0.2 to 2.3+/-0.2 L/min; P<0.05) and renal blood flow (131+/-17 to 162+/-18 mL/min; P<0.05) increased. Glomerular filtration rate was maintained. There were no changes in plasma renin activity, angiotensin II, or aldosterone. NTG mediated similar hemodynamic changes and additionally decreased right atrial pressure and pulmonary vascular resistance. CONCLUSION: The new sGC stimulator BAY 41-2272 potently unloaded the heart, increased cardiac output, and preserved glomerular filtration rate without activation of the renin-angiotensin-aldosterone system in experimental CHF. These beneficial properties make direct sGC stimulation with BAY 41-2272 a promising new strategy for the treatment of cardiovascular diseases such as CHF.
Boerrigter et al. (Tue,) conducted a other in Congestive heart failure (canine model) (n=14). BAY 41-2272 vs. Nitroglycerin (1 and 5 micro g x kg(-1) x min(-1)) was evaluated on Cardiorenal and humoral function. In a canine model of heart failure, BAY 41-2272 significantly reduced mean arterial pressure (113 to 94 mm Hg; P<0.05) and increased cardiac output (2.1 to 2.3 L/min; P<0.05).