[Effects of urotensin II on isolated rat hearts under normal perfusion and ischemia reperfusion].
To shed light on cardiac effects of the potent vasoconstrictive peptide urotensin II (U II), Langendorff-perfused isolated rat hearts were consecutively perfused with 0.1, 1 and 10 nmol/L U II, for 5 min at each dose, followed by 5-min washout. Moreover, isolated hearts subjected to 20-min global no-flow ischemia were reperfused with U II (1 or 10 nmol/L) for 20 min. Heart function parameters including heart rate, left ventricular pressure and dP/dt were monitored; content of protein and myoglobin, and activity of lactate dehydrogenase (LDH) in coronary effluent were determined; malondialdehyde (MDA) in myocardium and [(125)I]-U II binding sites in plasma membrane were measured after the completion of perfusion. The results showed that: (1) In normal rat hearts, the coronary flow was decreased and the heart function was suppressed by U II dose-dependently, and these changes were not abolished by washout. The leakage of cardiac protein, myoglobin and LDH increased with the increment of U II, but it diminished rapidly after washout. In contrast, MDA content in U II -treated myocardium was not statistically different from that in normal myocardium. (2) Ischemia-reperfusion caused significant decreases in coronary flow, suppression of heart function, and leakage of protein and LDH. In U II -reperfused hearts, all these disorders were significantly aggravated and myocardial MDA content significantly increased (P<0.01), to a greater extent in the presence of higher dose of U II. (3) The maximal binding capacity (B(max)) of U II receptors in plasma membrane from ischemia-reperfusion myocardium increased significantly as compared with that of normal myocardium (20.53+/-1.98 vs 14.65+/-1.78 fmol/mg pr, P<0.01), while Kd remained unchanged. These results indicate that U II caused injury to the isolated rat hearts under normal perfusion, and worsened the injury of the hearts under ischemia-reperfusion, in which U II receptors were up-regulated.
Zhou
Ping
P
Cardiovascular Institute, First Hospital, Peking University, Beijing 100034.
Wu
Sheng-Ying
SY
Yu
Cheng-Fan
CF
Wang
Hua
H
Tang
Chao-Shu
CS
Lin
Li
L
Yuan
Wen-Jun
WJ
D000818:Animals; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014579:Urotensins / Q000494:pharmacology*
D014579:Urotensins; C029677:urotensin II