Lack of an effect of nephron-specific deletion of adenylyl cyclase 3 on renal sodium and water excretion or arterial pressure.
Adenylyl cyclase (AC)-stimulated cAMP plays a key role in modulating transport and channel activity along the nephron. However, the role of individual adenylyl cyclase isoforms in such regulation is largely unknown. Since adenylyl cyclase 3 (AC3) is expressed throughout nephron, we investigated its role in the physiologic regulation of renal Na(+) and water transport. Mice were generated with inducible nephron knockout of AC3 (AC3 KO) by breeding mice with loxP-flanked critical exons in the Adcy3 gene with mice expressing Pax8-rtTA and LC-1 transgenes. After doxycycline treatment at 1 month of age, nephron AC3 KO mice had 100% Adcy3 gene recombination in all renal tubule segments, but not in glomeruli. Sodium intake, urinary Na(+) excretion, glomerular filtration rate, and blood pressure were similar between nephron KO mice and the controls during normal, high, and low Na(+) diets. Plasma renin concentration was not different between the two groups during varied Na(+) intake. Moreover, there were no differences in urine volume and urine osmolality between the two genotypes during normal or restricted water intake. In conclusion, these data suggested that AC3 is not involved in the physiological regulation of nephron Na(+) and water handling.
Division of Nephrology, University of Utah Health Sciences Center Salt Lake City Veterans Affairs Medical Center, Salt Lake City, UT.
Wararat
W
Kittikulsuth
Division of Nephrology, University of Utah Health Sciences Center Salt Lake City Veterans Affairs Medical Center, Salt Lake City, UT.
Deborah
D
Stuart
Division of Nephrology, University of Utah Health Sciences Center Salt Lake City Veterans Affairs Medical Center, Salt Lake City, UT.
Alfred N
AN
Van Hoek
Division of Nephrology, University of Utah Health Sciences Center Salt Lake City Veterans Affairs Medical Center, Salt Lake City, UT donald.kohan@hsc.utah.edu.
Donald E
DE
Kohan
Adenylyl cyclase 3; blood pressure; nephron; sodium excretion, water excretion