Alterations in pharmacological action of the right ventricle of monocrotaline-induced pulmonary hypertensive rats.
The present study was undertaken to elucidate pathophysiological and pharmacological alterations in the right ventricle in monocrotaline-administered (MCT) rats. Examination of tissue weights of the MCT and age-matched control (CON) rats indicated the right ventricular (RV) hypertrophy until 8 weeks after a single subcutaneous administration of 60 mg/kg MCT. Apparent fibrosis in the right ventricle of the MCT rat at the 6th week (6w-MCT) was observed. Echocardiographic measurement of the cardiac and hemodynamic parameters of the MCT rat showed decreases in cardiac output and stroke volume indices at the 6th and 8th weeks. The RV Tei index, which increase represents aggravation of RV function, was augmented at the 4th to 8th week. The results suggest the genesis of cardiac and RV failure until 6 weeks after MCT administration. Injection of dobutamine (300 ng) or colforsin daropate (1 microg) into the perfused right ventricle isolated from CON rat at the 6th week resulted in a marked increase in cardiac double product, whereas injection of either agent into the right ventricle from the 6w-MCT rat elicited a small increase in the double product, followed by a sustained decrease in the developed tension. Infusion of acetylcholine (1 microg) into the RV muscle of the 6w-MCT rat resulted in prolongation of the periods for cardiac arrest and for bradycardia of the right ventricle. The results suggest that MCT administration causes the RV hypertrophy and eventually leads to the RV failure, accompanied by abnormal inotropic and chronotropic actions of the RV muscle.
Daicho
Takuya
T
Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
Yagi
Tatsuya
T
Takano
Saori
S
Marunouchi
Tetsuro
T
Abe
Yohei
Y
Ohara
Meiko
M
Takeo
Satoshi
S
Tanonaka
Kouichi
K
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004562:Electrocardiography; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D016686:Monocrotaline / Q000633:toxicity*; D009200:Myocardial Contraction / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D016278:Ventricular Function, Right / Q000187:drug effects*
D002316:Cardiotonic Agents; D016686:Monocrotaline