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We tested the hypothesis that atrial natriuretic factor (ANF) may play a role in the development of hypertension in salt-sensitive Dahl (S) rats as compared to normotensive salt-resistant Dahl (R) rats. We measured immunoreactive ANF in plasma and atria of the inbred (JR) strain of Dahl S and R rats receiving 0.9 or 8% NaCI diets for up to 8 weeks. We also tested the effect of acute volume expansion on plasma and atrial ANF values in rats receiving the 0.9% salt diet. In addition, we examined the effects of exogenous ANF in the form of atriopeptin III given as intravenous bolus infusion at both levels of salt intake. We found no difference in plasma and atrial values between S and R rats irrespective of salt intake. The S and R rats showed a similar, five- to sevenfold increase of plasma ANF in response to acute saline expansion. Finally, we were unable to demonstrate differences between S and R rats in response to atriopeptin III with respect to transient decreases in blood pressure, and pronounced increases in glomerular filtration rate (GFR), renal blood flow or natriuresis. These results do not reveal appreciable changes in the ANF system of Dahl S rats either before or after onset of hypertension when compared to normotensive R rats. Therefore, our findings do not support the notion that ANF is important in the development or maintenance of chronic salt-induced hypertension in S rats.