It is unknown whether atrial natriuretic factor (ANF) is a mediator of environmental salt tolerance in euryhaline teleost fish. This was investigated in anesthetized Gila atraria, a euryhaline teleost native to springs of pleistocene Lake Bonneville. Plasma levels of immunoreactive (ir) ANF [using anti-human ANF-(99-126) antibodies] in fish obtained from a "fresh water" spring were significantly lower (146 +/- 27) than those in fish obtained from a "1% NaCl" spring (347 +/- 21 pg/ml, P less than 0.01). Electron micrographs of fish atrial and ventricular cardiocytes demonstrated many perinuclear granules, which closely resembled ANF-containing secretory granules seen in mammalian atriocytes. Fish heart extract contained ANF-like material of 3 kDa, which caused a marked diuresis and natriuresis in rats. In a second study, fish from a 1% NaCl spring were kept in tanks. One-third of the fish were maintained in 1% NaCl and one-third each were either adapted to fresh- or high-salt water. After 12 days, plasma irANF levels in 1% NaCl fish were 343 +/- 55, in fresh water fish 213 +/- 20 and in high-NaCl fish 691 +/- 79 pg/ml. These values differed significantly from each other (P less than 0.01). There was a close correlation between plasma irANF levels and both environmental and internal salt concentration. These data suggest that piscine ANF is an as yet unrecognized mediator of salt tolerance in this teleost and that ANF in these animals closely resembles mammalian ANF.
We examined whether replacement of cardiac atria and ventricles with total artificial hearts (TAH), a procedure that removes cardiac nerves and all sources of atrial natriuretic factor (ANF), would cause alterations in volume homeostasis in awake calves. Preoperatively, extracted plasma immunoreactive (ir)ANF levels were 13.3 +/- 0.6 and remained postoperatively at 10.5 +/- 0.4 pg/ml (P less than 0.01). TAH implantation caused systemic and pulmonary hypertension (P less than 0.01), salt retention, edema, and significant elevations of plasma renin, aldosterone, and arginine vasopressin. In intact calves rapid infusion of 6 liters of normal saline raised irANF levels to 73.7 +/- 6.5 pg/ml (P less than 0.01) and elicited a large natriuresis and diuresis. No such response to 6 liters of normal saline was obtained after calves had recovered from TAH implantation. Reduction of cardiac output (CO) by 50% caused further salt retention and no change in irANF levels. Elevation of CO back to and 33% above base line produced only a diuresis, whereas salt retention persisted and irANF levels remained unchanged. The same maneuvers elicited in surgical control calves (artificial ventricles only, largely intact atria) a significant increase in irANF levels and a diuresis and natriuresis. In conclusion, alterations in volume homeostasis observed after TAH implantation seem to be the consequence of at least two pathophysiological mechanisms: 1) functional ANF "deficiency," characterized by apparently unregulated ANF secretion from noncardiac sites, and 2) cardiac denervation.
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