Ultrastructural immunolocalization of the atrial natriuretic factor pathways in fetal, neonatal, and adult Syrian hamsters: from the atrial cardiomyocytes to the circulation via the endocardium, atrial capillaries and epicardium.

Atrial natriuretic factor (ANF)-immunoreactivity was identified with peroxidase-antiperoxidase staining and immunoelectron microscopic gold labeling techniques in atrial tissues of fetal, newborn and adult Syrian hamsters. ANF-immunoreactive (ANF-IR) material was present in electron dense granules of the atrial myocytes with a diameter between 150 and 190 nm. In addition, ANF was observed in the extracellular lumen of omega-shaped profiles of the sarcolemma of atrial myocytes where the atrial granules fuse with this sarcolemma, in the endomysial spaces next to the atrial myocytes, and in association with the endocardial endothelial cells. ANF-IR material was detected in the perivascular spaces and the blood vessel endothelia of the oldest atria. In these endothelia, immunolabeling was detected at the basal surfaces of the plasma membrane, in clear vesicles, in the apical surface membrane. ANF-IR product is also observed at the level of the basal lamina, in vacuoles, in apical crypts, and at the surface of the epicardial cells. Our results complement previous data and biochemical findings demonstrating that pro-ANF is released by the atrial myocytes via exocytosis (emiocytosis). After diffusion through the subendocardial and subepicardial space, the atrial peptide is then transported through the endocardial, epicardial, and blood vessel endothelia into the blood by a receptor-mediated endocytosis mechanism. Our observations suggest that the endothelial linings of the heart atria could play an important role in the control of transport, in activating the prohormone, and in the secretion of active ANF into the blood.