Recent investigations have provided considerable evidence showing that 1) atrial natriuretic factor (ANF) is secreted by the heart in response to atrial stretch and 2) administration of ANF affects renal salt and water excretion, blood pressure, and the concentration of other hormones such as renin, aldosterone, and vasopressin. However, these studies have not demonstrated a cause and effect relationship between ANF release and sodium excretion or blood pressure regulation. Furthermore, most of these studies have been carried out in rats or dogs and relatively little is known about the effects of ANF on the nonhuman primate. The purpose of the proposed studies is to further clarify the importance of ANF in the conscious monkey by determining not only the sensitivity of this species to ANF but, more importantly, the contribution of endogenous increases in ANF on cardiovascular regulation by using atrial appendectomy (which attenuates ANF release) or passive immunization with antisera directed against ANF to reduce circulating ANF levels.
The specific aims are: 1) to determine the threshold concentration of ANF that affects renal salt and water excretion, systemic hemodynamics, and other cardiovascular hormones (renin, aldosterone, and vasopressin) and whether this threshold changes during hypervolemic conditions; 2) to determine the effects of passive immunization (administration of antisera containing antibodies against ANF) on endogenous ANF levels, the renal response to volume expansion, and the time course for these changes; 3) to determine whether ANF has a tonic or basal effect on systemic hemodynamics and whether endogenous changes in ANF contribute to the dynamic cardiovascular responses to central blood volume expansion; 4) to determine whether administration of physiologic levels of ANF influences baroreceptor control of heart rate and whether physiologically induced elevations in ANF influence this reflex; 5) to determine the necessity or contribution of the renal nerves in mediating the renal response to ANF administration; and 6) to determine the role of ANF in mediating mineralocorticoid escape. Results from these studies may suggest altered mechanisms in the pathogenesis of certain disease states including congestive heart failure and hypertension.
| Benjamin, B A; Peterson, T V (1994) Effect of bilateral atrial appendectomy on postprandial sodium excretion in conscious monkeys. Proc Soc Exp Biol Med 206:45-52 |
| Peterson, T V; Benjamin, B A (1992) The heart and control of renal excretion: neural and endocrine mechanisms. FASEB J 6:2923-32 |
| Peterson, T V; Benjamin, B A; Hurst, N L et al. (1991) Renal nerves and postprandial renal excretion in the conscious monkey. Am J Physiol 261:R1197-203 |
