Long-term treatment with nipradilol, a nitric oxide-releasing beta-adrenergic blocker, enhances postischemic recovery and limits infarct size.
BACKGROUND
This study examines whether the chronic administration of nipradilol, a nitric oxide-releasing beta-adrenergic blocker, decreases ischemia-reperfusion injury.


METHODS
Rats were treated with nipradilol (10 mg/kg per day orally) or a vehicle alone for 4 weeks. Isolated rat hearts were assigned to one of five groups (each n = 6): global ischemia groups treated with the vehicle or with nipradilol were subjected to 20 minutes of ischemia; ischemic preconditioning groups treated with the vehicle or with nipradilol were subjected to 3 minutes of ischemic preconditioning; and the L-arginine group treated with the vehicle received 1 mmol/L of L-arginine before global ischemia. Hemodynamic variables and coronary flow were recorded continuously. Nitrites and nitrates levels were measured 60 minutes after reperfusion, and the infarct size was determined. In another series (each n = 6), lipid peroxidation was investigated.


RESULTS
In the nipradilol group, significant preservation of the left ventricular pressure and coronary flow, as well as the level of nitrates and nitrites, was observed, compared with the global ischemia group. The infarct size was also significantly reduced in the ischemic preconditioning (23.5%+/-5.47%), L-arginine (25.6%+/-5.59%), and especially the nipradilol (10.7%+/-1.65%) groups. However, in the nipradilol plus ischemic preconditioning group, the protective effects were eliminated. Lipid peroxidation after nipradilol treatment was significantly reduced before and after global ischemia, compared with the global ischemia group.


CONCLUSIONS
The chronic administration of nipradilol improves postischemic functional recovery and infarct size, partly by preventing the formation of lipid peroxides. These cardioprotective effects were, however, abolished by ischemic preconditioning.
Suematsu
Yoshihiro
Y
Department of Cardiothoracic Surgery, University of Tokyo, Japan. suematsu@aurora.dti.ne.jp
Ohtsuka
Toshiya
T
Horimoto
Hitoshi
H
Maeda
Katsuhide
K
Nakai
Yasunari
Y
Mieno
Shigetoshi
S
Takamoto
Shinichi
S
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011412:Propanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C036089:nipradilol