Hypothyroid dependent myocardial angiotensin receptor trafficking is involved in improved cardiac performance after heat acclimation.
OBJECTIVE
The renin-angiotensin system (RAS) plays a key role in heat acclimation, a process which induces adaptive changes in cardiac function. These changes are mediated in part by reduced thyroid hormone activity and improve myocardial function during and following exposure to various (non-heat) stresses such as ischemia. The aim of this study was to examine the role of RAS in the development of the heat acclimated protected heart.


METHODS
Three treatment groups were used: (1) C, controls; (2) AC, heat acclimated rats (1mo 34 degrees C,); and (3) HAEL, heat acclimated euthyroid rats treated with 3ng/ml of eltroxine. A Langendorff perfusion apparatus was used to measure hemodynamic parameters at baseline and following administration of angiotensin-II, losartan and PD123319 in isolated hearts. Protein and mRNA levels of angiotensin receptors were measured.


RESULTS
Both C and HAEL animals showed increased contractility and a drop in coronary flow during angiotensin II exposure whereas AC animals did not have an inotropic response or vasoconstriction. Significantly different patterns of AT1 and AT2 receptor densities (a 50% reduction and a 30% increase in outer cell membrane AT1 and AT2 receptors respectively) were observed in AC animals compared to the other two groups. AT receptor mRNA levels were similar in all treatment groups.


CONCLUSIONS
The attenuated response of heat acclimated hearts to angiotensin is mediated by reduced thyroxine levels and is associated with a shift in AT1 receptors from the outer to the inner membrane. This shift appears to be caused by modified posttranslational trafficking of AT receptors.
Durst
Ronen
R
Cardiology Division, Hadassah Hebrew University Medical Center, Jerusalem, Israel. rdurst@partners.org
Goldstein
Kobi
K
Horowitz
Yuval
Y
Baggish
Aaron
A
Gare
Meir
M
Hasin
Yonathan
Y
Lotan
Chaim
C
Horowitz
Michal
M
D000064:Acclimatization / Q000187:drug effects / Q000502:physiology*; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D006358:Hot Temperature / Q000009:adverse effects*; D007037:Hypothyroidism / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism
D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000804:Angiotensin II