Thyrotropin-releasing hormone in rat heart: effect of swelling, angiotensin II and renin gene.
OBJECTIVE
This study was performed to examine thyrotropin-releasing hormone (TRH) secretion and regulation in rat heart.


METHODS
Expression of prepro-TRH gene in left atrium and left ventricle was studied by RT-PCR. TRH secretion from slices of left auricle and left ventricle in response to cell swelling (induced by hypotonic medium or ethanol in isosmotic medium), angiotensin II and losartan and their combinations was studied.


RESULTS
RT-PCR revealed two times higher prepro-TRH expression in left auricle than left ventricle. In transgenic rats with extra copy of mouse renin gene a marked increase of prepro-TRH expression in the heart was noted but the relative difference between left atrium and left ventricle persisted. The swelling stimulated TRH release from both left auricle and left ventricle and this stimulation could not be inhibited by bumetanide. Angiotensin II (10 nmol L-1) added into medium significantly decreased basal secretion of TRH. The inhibiting effect of Angiotensin II was prevented by 1 micromol L-1 losartan, an angiotensin II AT1 receptor blocker. When angiotensin II and hypotonicity were applied simultaneously, swelling-induced secretion persisted.


CONCLUSIONS
TRH secretion from heart slices has attributes of regulated secretion--depending on the stimulus it could be either stimulated or inhibited. Renin positively affects prepro-TRH expression in the heart. Angiotensin II inhibits TRH secretion from heart tissue by a mechanism involving AT1 receptors. Swelling-induced TRH secretion overrides inhibitory effect of angiotensin II. Swelling could be a useful tool when natural or pharmacological secretagogue is unknown. Peptides and proteins released by swelling could be mediators of local and remote ischaemic preconditioning protecting from subsequent ischaemia.
Bacova
Z
Z
Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Baqi
L
L
Benacka
O
O
Payer
J
J
Krizanová
O
O
Zeman
M
M
Smreková
L
L
Zorad
S
S
Strbák
V
V
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D002034:Bumetanide / Q000494:pharmacology; D048429:Cell Size; D000431:Ethanol / Q000494:pharmacology; D015870:Gene Expression; D006321:Heart / Q000187:drug effects / Q000378:metabolism*; D006352:Heart Ventricles; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051379:Mice; D011498:Protein Precursors / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects; D012083:Renin / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013268:Stimulation, Chemical; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D014882:Water-Electrolyte Balance / Q000187:drug effects
D011498:Protein Precursors; D044140:Receptor, Angiotensin, Type 1; D002034:Bumetanide; C063596:prepro-thyrotropin-releasing hormone; D000804:Angiotensin II; D000431:Ethanol; D013973:Thyrotropin-Releasing Hormone; D012083:Renin; D019808:Losartan