The secretion of atrial natriuretic peptide by the heart is not simply the arterial-coronary sinus concentration difference times coronary blood flow, because only a small fraction of total coronary blood flow passes through the atria. We measured coronary sinus and arterial plasma atrial natriuretic factor (ANF) concentrations and blood flow to each part of the heart using the radioactive microsphere technique. Before acute volume expansion, the arterial-coronary sinus ANF difference was

more »

... pg/ml and rose to 1,009±220 pg/ml during volume expansion, whereas total coronary blood flow rose from 167 to 465 mllmin. Atrial blood flow rose from 2.9%o to 4.6% of total coronary blood flow during volume expansion. ANF secretion rate increased from 51 to 469 ng/min. When divided by atrial weight, ANF secretion rate increased from 4.0±.0.3 to 56±12 ng/min/g atrial tissue -in other words, from 0.3% to 3.7% of tissue ANF content each minute. Dividing by atrial blood flow indicated that the concentration of ANF leaving atrial tissue was 10,000 to 29,651 pg/ml, and the additional secretion of ANF was determined by the increase in coronary blood flow. Therefore, at least two mechanisms are responsible for altering coronary sinus ANF and circulating ANF: the release rate from atrial myocytes and the washout via changes in atrial blood flow. (Circulation Research 1990;67:609-614) Secretion of atrial natriuretic factor (ANF) from the heart can be estimated by the product of the arterial-venous concentration difference across the coronary circulation and coronary blood flow. This calculation implies that ANF is produced uniformly within the heart, whereas ANF is produced primarily in the atrial appendages of normal heart.1-4 ANF is a circulating hormone rather than a local one; therefore, many physiological studies, including our own,1 related to volume or cardiovascular homeostasis, such as during acute volume expansion and hypertension, have focused on circulating atrial peptide concentrations.5 However, to determine the mechanisms of atrial peptide secretion and the alterations that might occur in diseased states, such as heart failure, in which plasma ANF rises dramatically,6'7 it is essential 1 j understand the dynamics of atrial peptide secretion from the atria and how this is coupled to changes in atrial function and coronary blood flow regulation. From the Department of Physiology, New York Medical College, Valhalla, N.Y. A recent study by Hirata et a18 has reported coronary sinus ANF concentrations in patients on the order of 500 pg/ml/m2 and ANF secretion rates on the order of 14 ng/min/m2. Because ANF, which is secreted by the normal heart, comes from the atria, and atrial blood flow is only a small fraction of blood flow through the whole heart, the ANF concentration in the coronary sinus only partially reflects the dynamic changes in ANF secretion rate that occur in the atria. This concept is important not only to understand the dynamics of atrial peptide secretion but also to understand the control of atrial peptide synthesis, because some authors have proposed that ANF secretion may exceed ANF synthesis, leading to a decrease in the content of ANF or granularity in the atria.9,10 Therefore, the goals of the current study were 1) to determine the arterial-coronary sinus ANF difference, coronary blood flow, and blood flow to each structure of the heart, particularly the atria and atrial appendages, and 2) to determine the changes in ANF secretion rate by atrial tissue that occurs during acute dramatic volume expansion in the conscious dog. Materials and Methods Surgical Preparation All experiments were performed in chronically instrumented conscious dogs. The animals were preanesthetized with acepromazine (1 mg/kg) and anes-by guest on