Cardiac atria are the primary source of ANP release in hypoxia-adapted rats.
OBJECTIVE
atrial natriuretic peptide (ANP) is released from the heart in response to hypoxia and helps mitigate the development of pulmonary hypertension. However, the mechanism of hypoxia-induced ANP release is not clear. The cardiac atria are the primary source of ANP secretion under normal conditions, but right ventricular ANP expression is markedly up-regulated during adaptation to hypoxia. We sought to better understand mechanisms of cardiac ANP release during adaptation to hypoxia.


METHODS
we measured hypoxia-induced ANP release from isolated perfused rat hearts obtained from normoxia and hypoxia-adapted rats before and after removal of the atria.


RESULTS
in both normoxia- and hypoxia-adapted hearts, ANP levels in the perfusate increased within 15 min of hypoxia. Hypoxia-induced ANP release was greater from hypoxia-adapted than normoxia-adapted hearts. Baseline and hypoxia-induced ANP release were considerably greater with the atria intact (213±29 to 454±62 and 281±26 to 618±87 pg/ml for normoxia- and hypoxia-adapted hearts respectively, P<0.001 for both) than with atria removed (94±17 to 131±32 and 103±26 to 201±55 pg/ml, respectively, P<0.002 for both). Hypoxia-induced ANP release was reduced over 80% by removing the atria in both normoxia- and in hypoxia-adapted hearts. Acute hypoxia caused a transient increase in lactate release and reductions in pH and left ventricular generated force, but no differences in pH or left ventricular generated force were seen between normoxia- and hypoxia-adapted rats.


CONCLUSIONS
we conclude that the right ventricle is not a major source of cardiac ANP release in normoxia- or hypoxia-adapted rats.
Casserly
Brian
B
Division of Pulmonary Medicine, Memorial Hospital of Rhode Island, Pawtucket, RI, United States.
Pietras
Linda
L
Schuyler
Joy
J
Wang
Richard
R
Hill
Nicholas S
NS
Klinger
James R
JR
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001835:Body Weight; D002118:Calcium / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006325:Heart Atria / Q000378:metabolism* / Q000601:surgery; D006863:Hydrogen-Ion Concentration; D017380:Hypertrophy, Right Ventricular / Q000473:pathology; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology; D017725:Ventricular Pressure / Q000502:physiology
D019344:Lactic Acid; D009320:Atrial Natriuretic Factor; D012964:Sodium; D005947:Glucose; D011188:Potassium; D002118:Calcium