title: Effects of Single Drug and Combined Short-term Administration of Sildenafil, Pimobendan, and Nicorandil on Right Ventricular Function in Rats With Monocrotaline-induced Pulmonary Hypertension.
abstract: This study was designed to assess the progression of pulmonary arterial hypertension (PAH) and the effectiveness of therapy using recently investigated echocardiographic parameters. PAH is characterized by the progressive elevation of pulmonary artery pressure and right ventricular hypertrophy and dysfunction, which ultimately results in right-sided heart failure and death. Echocardiography results and invasive measurements of right and left ventricular systolic pressures were compared after 3-week administrations of sildenafil (S group), pimobendan (P group), nicorandil (N group), and their combinations (SP and SPN groups) in male rats with monocrotaline (MCT)-induced pulmonary hypertension (M group) and without this condition (C group). The groups that received pimobendan alone and in combinations (SP and SPN groups) showed improvement in their echocardiographic parameters of systolic function. A significant improvement of diastolic function was achieved in the SPN group. Invasive measurements showed the most significant decreases of right ventricular systolic pressure in the N and SPN groups, and the use of pimobendan resulted in a comparatively low risk of adverse hemodynamic effects (left ventricular systolic pressure). Although our results suggested the attenuation of PAH severity in all treatment groups, PAH could not be reversed.
authors: Department of Veterinary Surgery, Faculty of Veterinary Medicine, Tokyo University of Agriculture and Technology (TUAT), Tokyo, Japan.
authors: Telma M
authors: TM
authors: Nakata
authors: Ryou
authors: R
authors: Tanaka
authors: Rieko
authors: R
authors: Yoshiyuki
authors: Toshiharu
authors: T
authors: Fukayama
authors: Seijiro
authors: S
authors: Goya
authors: Ryuji
authors: R
authors: Fukushima
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D016686:Monocrotaline; D020108:Nicorandil / Q000494:pharmacology*; D058987:Phosphodiesterase 3 Inhibitors / Q000494:pharmacology; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D017208:Rats, Wistar; D020127:Recovery of Function; D012720:Severity of Illness Index; D000068677:Sildenafil Citrate / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D018497:Ventricular Dysfunction, Right / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D016278:Ventricular Function, Right / Q000187:drug effects*
chemical_list: D058987:Phosphodiesterase 3 Inhibitors; D058986:Phosphodiesterase 5 Inhibitors; D011724:Pyridazines; D014665:Vasodilator Agents; D020108:Nicorandil; C041648:pimobendan; D016686:Monocrotaline; D000068677:Sildenafil Citrate