Thyrotropin-releasing hormone is induced in the left ventricle of rats with heart failure and can provide inotropic support to the failing heart.
BACKGROUND
We reported previously that left ventricular gene expression for thyrotropin-releasing hormone (TRH) precursor was increased in rats with heart failure 8 weeks after myocardial infarction (MI) and that early ACE inhibition tended to cause further myocardial induction of this gene.


RESULTS
Here, we show that after MI, the expression of pro-TRH is induced in the heart coordinately with the protease PC1, an important enzyme in TRH biosynthesis. Pro-TRH gene expression was induced in cardiac interstitial cells after MI, and this effect was restricted to the heart, because no increase in TRH mRNA abundance was observed in the hypothalamus, kidney, or lung. Transcript abundance of pro-TRH can be increased in cultured cardiac fibroblasts by several adrenergic agonists, indicating that the adrenergic axis may play a regulatory role in cardiac TRH production. Acute intravenous administration of TRH to rats with ischemic cardiomyopathy caused a significant increase in heart rate, mean arterial pressure, cardiac output, stroke volume, and cardiac contractility.


CONCLUSIONS
Taken together, these results indicate that TRH is specifically induced in the heart after MI and that it can increase cardiac performance in rats with ischemic cardiomyopathy. Thus, in addition to catecholamine and angiotensin II, pro-TRH/TRH may be another important axis that affects hemodynamics and cardiac function in heart failure.
Jin
Hongkui
H
Genentech, Inc, 1 DNA Way, South San Francisco, Calif 94080, USA. hkj@gene.com
Fedorowicz
Grazyna
G
Yang
Renhui
R
Ogasawara
Annie
A
Peale
Franklin
F
Pham
Thinh
T
Paoni
Nicholas F
NF
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D006352:Heart Ventricles / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015425:Myocardial Reperfusion; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D045664:Proprotein Convertase 1 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D002316:Cardiotonic Agents; D012333:RNA, Messenger; D013973:Thyrotropin-Releasing Hormone; D045664:Proprotein Convertase 1