Noncoordinate regulation of alpha-1 adrenoreceptor coupling and reexpression of alpha skeletal actin in myocardial infarction-induced left ventricular failure in rats.
To determine the effects of myocardial infarction-induced left ventricular failure on the regulation of surface alpha-1 adrenoreceptors and signal transduction, large infarcts were produced in rats and the animals killed seven days later. After the documentation of impaired left ventricular pump performance, radioligand binding studies of the alpha-1 adrenoreceptor, norepinephrine-stimulated phosphoinositol turnover, and ADP ribosylation of 41 kD substrate by pertussis toxin were examined in the hypertrophying unaffected myocardium. Moreover, the expression of sarcomeric actin isoforms was analyzed by Northern blots and hybridization with specific oligonucleotide probes. Alpha-1 adrenoreceptor density was found not to be altered in membranes obtained from the spared left ventricular tissue, whereas phosphoinositol turnover was increased 3.1-fold in the viable myocytes of infarcted hearts. Furthermore, pertussis toxin substrate was augmented 2.5-fold in membranes prepared from the surviving left ventricular myocardium. Finally, an upregulation of the skeletal actin isoform was detected in the tissue of the failing left ventricle. In conclusion, the possibility is raised that in the presence of severe myocardial dysfunction and ongoing reactive hypertrophy, effector pathways linked to the alpha-1 adrenoreceptor may stimulate the myocyte hypertrophic response which would tend to normalize cardiac hemodynamics. The reexpression of alpha skeletal actin may be a molecular indicator of the persistance of an overload on the myocardium.
Meggs
L G
LG
Department of Medicine, New York Medical College, Valhalla 10595.
Tillotson
J
J
Huang
H
H
Sonnenblick
E H
EH
Capasso
J M
JM
Anversa
P
P
D000199:Actins / Q000096:biosynthesis* / Q000235:genetics; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002303:Cardiac Output, Low / Q000378:metabolism; D006332:Cardiomegaly; D006439:Hemodynamics; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D009929:Organ Size; D037342:Pertussis Toxin; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000199:Actins; D007295:Inositol Phosphates; D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D037342:Pertussis Toxin; D009638:Norepinephrine