ANGIOTENSINOGEN GENE NULL-MUTANT MICE LACK HOMEOSTATIC REGULATION OF GLOMERULAR-FILTRATION AND TUBULAR REABSORPTION

Chronic volume depletion by dietary salt restriction causes marked dec rease in glomerular filtration rate (GFR) with little increase in urin e osmolality in angiotensinogen gene null mutant (Agt(-/-)) mice. More over, urine osmolality is insensitive to both water and vasopressin ch allenge. In contrast, in normal wild-type (Agt(+/+)) mice, GFR remains remarkably constant and urine osmolality is adjusted promptly. Change s in volume status also cause striking divergence in renal structure b etween Agt(-/-) and Agt(+/+) mice. Thus, in contrast to the remarkably stable glomerular size of Agt(+/+) mice, glomeruli of Agt(-/-) mice a re atrophied during a low salt and hypertrophied during a high salt di et. Moreover, the renal papilla, a structure unique to mammals and ess ential for urine diluting and concentrating mechanisms, is hypoplastic in Agt(-/-) mice. Thus, angiotensin is essential for the two fundamen tal homeostatic functions of the mammalian kidney, namely stable GFR a nd high urine diluting and concentrating capacity during alteration in extracellular fluid (ECF) volume. This is not only accompanied by ang iotensin's tonic effects on renal vasomotor tone and tubule transporte rs, but also accomplished through its capacity to affect the structure of both the glomerulus and the papilla directly or indirectly.