Atrial BNP endocrine function during chronic unloading of the normal canine heart

Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905 Submitted 5 July 2004 ; accepted in final form 22 September 2004 The goal of the study was to define the effect of chronic unloading of the normal heart on atrial endocrine function with a focus on brain natriuretic peptide (BNP), specifically addressing the role of load and neurohumoral stimulation. Although produced primarily by atrial myocardium in the normal heart, controversy persists with regard to load-dependent vs. neurohumoral mechanisms controlling atrial BNP synthesis and storage. We used a unique canine model of chronic unloading of the heart produced by thoracic inferior vena caval constriction (TIVCC), which also resulted in activation of plasma endothelin (ET-1), ANG II, and norepinephrine (NE), known activators of BNP synthesis, compared with sham. TIVCC was produced by banding of the inferior vena cava for 10 days ( n = 6), whereas in control ( n = 5) the band was not constricted (sham). In a third group ( n = 7), the band was released on day 11 , thus acutely reloading the heart. Chronic TIVCC decreased cardiac output and right atrial pressure with a decrease in atrial mass index consistent with atrial atrophy. Atrial BNP mRNA decreased compared with sham. Immunoelectron microscopy revealed an increase in BNP in atrial granules consistent with increased storage. Acute reloading increased cardiac filling pressures and resulted in an increase in plasma BNP. We conclude that chronic unloading of the normal heart results in atrial atrophic remodeling and in suppression of atrial BNP mRNA despite intense stimulation by ET, ANG II, and NE, underscoring the primacy of load in the control of atrial endocrine function and structure. atria; myocardial load; brain natriuretic peptide Address for reprint requests and other correspondence: O. Lisy, Cardiorenal Research Laboratory, Mayo Clinic and Foundation, 200 First St., SW, Rochester, MN, 55905 (E-mail: lisy.ondrej{at}mayo.edu )