Over a period of many years it has become apparent that the regulation of arterial pressure is intimately linked to body salt and water balance. Recently, it has been shown that the atria contain a potent natriuretic and blood pressure lowering substance which has been termed the atrial natriuretic factor (ANF). The long-term goals of this project are to obtain a better understanding of the role of ANF and other potential cardiac hormones in the regulation of kidney function, blood volume and blood pressure. Recent evidence suggests that in addition to ANF, other peptides formed from the pro-ANF molecule circulate in plasma. Specifically, pro-ANF (31-67) is present in plasma in higher concentrations than ANF and may have physiological effects similar to ANF. The goals of this project are: 1) to establish normal baseline values for pro-ANF (31-67) in rats on normal, low and high NaCl intakes, 2) to determine the effect of 5, 10 or 20% blood volume expansions on plasma pro-ANF (31-67) in anesthetized rats and compare these changes to changes in ANF, 3) to compare the effects of similar infused doses of ANF and pro-ANF (31-67) on renal function, plasma renin activity and blood pressure, 4) to examine the effect of pro-ANF (31-67) on renal flow, GFR, sodium chloride excretion, water excretion and renin secretion in the isolated perfused kidney, 5) to compare the secretion of pro-ANF (1-98), pro-ANF (31-67) and ANF (99-126) from isolated atria in response to: a) changes in atrial stretch and b) atrial pacing and 6) to test for a short-loop negative feedback effect of ANF or pro-ANF (31-67) on their own production by measuring pro-ANF (1-98) secretion as an end point in the isolated atria. Although numerous studies have focused on ANF, it is apparent that more information is needed on the relative importance the other portions of the pro-ANF molecule in the control of renal function and blood volume. Recent evidence suggests that these other atrial peptides, particularly pro-ANF (31-67), may have an important physiological role.
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