Enhanced early after-myocardial infarction concentration of TNF-alpha subsequently increased circulating and myocardial adrenomedullin in spontaneously hypertensive rats.
Both inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and the cardiac protective peptide adrenomedullin (AM) are increased in cardiac tissues and plasma in patients with myocardial infarction (MI) and chronic heart failure. Recently they have been increasingly recognized as important factors in the pathophysiology of MI and resultant congestive heart failure. Compared with sham-operated spontaneously hypertensive rats (SHR), we investigated myocardial immunoreactivity of TNF-alpha and AM and also their mutual relations in vivo in SHR+MI. Residual myocardial depression after MI was studied also in isolated perfused hearts. In chronic experiments, 24 and 48 h after permanent ligation of the descending anterior branch of the left coronary artery, we examined hemodynamics, plasma and myocardial peptide levels. Left ventricular function was assessed in isolated perfused hearts subjected to "global ischemia and reperfusion" and after induction of "calcium paradox". Circulating and myocardial TNF-alpha concentrations increased early after MI in SHR. Studies with global ischemia and calcium paradox in isolated heart showed early myocardial depression and calcium-dependent gradual increase of left-ventricular end-diastolic pressure. In the SHR+MI myocardial AM concentrations were increased 9- and 49-fold after respective 24 h and culminated 48 h following MI. Circulating and myocardial AM was increased in SHR+MI in association with TNFalpha-induced myocardial depression. The both studied cardiac parameters displayed the beneficial effect of the enhanced myocardial AM concentration.
Drímal
J
J
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, Slovakia. exfadrim@savba.sk
Knezl
V
V
Paulovicová
E
E
Drímal
D
D
D053607:Adrenomedullin / Q000097:blood / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism*; D016277:Ventricular Function, Left
D014409:Tumor Necrosis Factor-alpha; D053607:Adrenomedullin; D002118:Calcium