In non-mammalian vertebrates, GFR functions as an ECF volume-regulatory mechanism while toxic nitrogenous wastes are excreted by non-glomerular organs(e.g., gills). In mammals, however, nitrogenous wastes are excreted exclusively through the glomerulus, and GFR is maintained constant during acute changes in ECF volume. Ang has been implicated to be intermediary to this GFR maintenance via its ability to affect the tubuloglomerular feedback system and to act as a potent efferent arteriolar constrictor. Morphological study of non-mammalian vertebrates undergoing chronic ECF volume expansion and contraction commonly reveals hypertrophic and atrophic glomeruli, respectively.

To study the glomerular morphology in mammals in chronic ECF volume changes, and the potential role of Ang, we examined the effect of high (H), normal (N) and low (L) dietary NaCl intake on the glomerular morphology of wild-type (Atg+/+) and homozygous mice carrying the angiotensinogen null-mutated gene (Atg-/-). The animals were placed on a respective dietary regimen after the completion of weaning (3 week old) until 8 weeks postnatally. In Atg-/- mice, we observed a phenomenon characteristic of non-mammalian vertebrates: In the Atg-/- mice on H, the glomerulus became markedly hypertrophied, while, in the Atg-/- on L, it became atrophied, and the size in Atg-/- mice on N was intermediate. In contrast, the glomerular size was unaffected by the salt intake in the wild-type, Atg+/+, mice. Thus, in marked contrast to other vertebrates, mammals maintain glomerular size during chronic ECF volume changes. Ang plays a pivotal role in this maintenance of glomerular size by abbrogating the powerful influence of ECF volume on the glomerular structure, an influence detrimental to this species, which is in constant need of the elimination of large amounts of toxic nitrogenous waste exclusively through the glomerulus.