A genetic model defines the importance of the atrial natriuretic peptide receptor (guanylyl cyclase-A) in the regulation of kidney function

Disruption of the atrial natriuretic peptide (ANP) receptor [guanylyl cycla se-A (GC-A)] gene yields mice with a salt-resistant form of hypertension, r aising fundamental questions on the role of ANP in acute regulation of the kidney. Here, we show that water intake, food consumption, stool weight, ur ine volume, and sodium excretion are not significantly different between wi ld-type and GC-A null mice on standard rodent chow (0.7% NaCl) or a high-sa lt diet (8% NaCl), In conscious mice with an indwelling catheter, the infus ion of a physiological saline solution containing 4% BSA resulted in a mark ed natriuresis/diuresis in wild-type mice but no response in GC-A null anim als, When physiological saline was given by gavage, however, the kidney res ponse of wild-type and null mice was equivalent, raising the possibility th at the gastrointestinal tract can directly regulate kidney function. Howeve r, administration of 0.9 % saline through an intraperitoneal route also res ulted in equal kidney responses in wild-type and null mice. When 0.9% NaCl lacking protein was infused i.v., wild-type and null mice both responded at the kidney level. Thus, GC-A appears dispensable for regulation of sodium; water excretion in response to changes in dietary sodium concentration, but likely becomes critical in volume expansions where the isooncotic pressure remains constant, such as head-out immersion or the initial and correctabl e stages of congestive heart failure.