Adenosine A1 receptor expression during the transition from compensated pressure overload hypertrophy to heart failure.
OBJECTIVE
Myocardial adenosine is increased in pressure-overload hypertrophy (POH) and exerts important cardioprotective effects that delay transition to left ventricular failure. Adenosine-mediated signaling is attenuated in POH, but whether this depends on receptor or postreceptor defects is unknown. We therefore examined left ventricular adenosine A1-receptor gene and protein expression in experimental POH.


METHODS
Six week-old Sprague-Dawley rats were subjected to abdominal aortic banding (group B) or sham operation (group S). Echocardiography and left ventricular catheterization were performed 10 weeks later under ketamine anesthesia. Left ventricular and lung weight indices were obtained postmortem. A1-Receptor mRNA and protein expression were measured in samples from left ventricular, right ventricular and aortic arch tissue. Group B rats were subgrouped as having compensated or decompensated hypertrophy according to the absence or presence of lung congestion (lung weight index below or above mean +/- 2SD compared with group S rats).


RESULTS
Both mRNA and protein A1-receptor expression were significantly increased in compensated group B versus group S rats (by, respectively, 37 and 77%; both P < 0.01). This was not observed in decompensated group B rats. No consistent gene or receptor expression changes were observed in right ventricular or aortic tissues.


CONCLUSIONS
In compensated POH, increased interstitial adenosine concentrations are accompanied by increased expression of the specific receptor mediating the major cardioprotective effects of this autacoid. Such overexpression is no longer detectable once the transition from POH to left ventricular failure has occurred. These observations may have pathophysiological and, in perspective, therapeutic relevance to the course of hypertensive heart disease.
Perlini
Stefano
S
Centro Interuniversitario Fisiologia Clinica e Ipertensione, Università di Milano, Milano-Bicocca e Pavia, Pavia, Italy. sperlini@unipv.it
Arosio
Beatrice
B
Parmeggiani
Luciano
L
Santambrogio
Daniela
D
Palladini
Giuseppina
G
Tozzi
Rossana
R
Gatti
Chiara
C
Annoni
Giorgio
G
Meyer
Theo E
TE
Ferrari
Alberto U
AU
D000818:Animals; D004195:Disease Models, Animal; D006333:Heart Failure / Q000235:genetics / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000235:genetics / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000378:metabolism*; D017725:Ventricular Pressure / Q000502:physiology
D012333:RNA, Messenger; D043682:Receptor, Adenosine A1