In this study we used HS-142-1, a novel non-peptide antagonist for the atrial natriuretic peptide (ANP) receptor, to clarify the possible physiological significance of ANP in acute hypervolemia. Substantial volume expansion in anesthetized rats induced a strong diuresis and natriuresis. These renal responses were significantly blocked by HS-142-1 at a dose of 3.0 mgkg-1 i.v. This observation suggests that ANP and its guanylyl cyclase-coupled receptor are, under the present conditions, physiologically involved that appears to be responsible for the renal responses in the volume homeostasis.
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